motor neurons

Summary

Summary: Neurons which activate muscle cells.

Top Publications

  1. ncbi Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Manuela Neumann
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 314:130-3. 2006
  2. ncbi Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation
    M E Gurney
    Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
    Science 264:1772-5. 1994
  3. ncbi Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis
    T J Kwiatkowski
    Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Science 323:1205-8. 2009
  4. ncbi Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6
    Caroline Vance
    Department of Clinical Neuroscience, King s College London, Medical Research Council MRC Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK
    Science 323:1208-11. 2009
  5. ncbi Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis
    Laura Ferraiuolo
    Academic Neurology Unit, Sheffield Institute for Translational Neuroscience, Department of Neuroscience, School of Medicine and Biomedical Sciences, University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UK
    Nat Rev Neurol 7:616-30. 2011
  6. ncbi Directed differentiation of embryonic stem cells into motor neurons
    Hynek Wichterle
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
    Cell 110:385-97. 2002
  7. ncbi Onset and progression in inherited ALS determined by motor neurons and microglia
    Severine Boillee
    Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Science 312:1389-92. 2006
  8. pmc Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model
    Yimin Hua
    Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
    Nature 478:123-6. 2011
  9. ncbi ALS: a disease of motor neurons and their nonneuronal neighbors
    Severine Boillee
    Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California, San Diego, La Jolla, California 92093, USA
    Neuron 52:39-59. 2006
  10. pmc Conversion of mouse and human fibroblasts into functional spinal motor neurons
    Esther Y Son
    Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    Cell Stem Cell 9:205-18. 2011

Detail Information

Publications378 found, 100 shown here

  1. ncbi Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Manuela Neumann
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 314:130-3. 2006
    ..TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders...
  2. ncbi Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation
    M E Gurney
    Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
    Science 264:1772-5. 1994
    ..The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS...
  3. ncbi Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis
    T J Kwiatkowski
    Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Science 323:1205-8. 2009
    ..Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders...
  4. ncbi Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6
    Caroline Vance
    Department of Clinical Neuroscience, King s College London, Medical Research Council MRC Centre for Neurodegeneration Research, Institute of Psychiatry, London SE5 8AF, UK
    Science 323:1208-11. 2009
    ..FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration...
  5. ncbi Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis
    Laura Ferraiuolo
    Academic Neurology Unit, Sheffield Institute for Translational Neuroscience, Department of Neuroscience, School of Medicine and Biomedical Sciences, University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UK
    Nat Rev Neurol 7:616-30. 2011
    ..Ongoing research on the cellular pathways highlighted in this Review is predicted to open the door to new therapeutic interventions to slow disease progression in ALS...
  6. ncbi Directed differentiation of embryonic stem cells into motor neurons
    Hynek Wichterle
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
    Cell 110:385-97. 2002
    ..induce mouse embryonic stem (ES) cells to differentiate into spinal progenitor cells, and subsequently into motor neurons, through a pathway recapitulating that used in vivo...
  7. ncbi Onset and progression in inherited ALS determined by motor neurons and microglia
    Severine Boillee
    Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Science 312:1389-92. 2006
    ..dismutase cause amyotrophic lateral sclerosis (ALS), a progressive paralytic disease characterized by loss of motor neurons. With the use of mice carrying a deletable mutant gene, expression within motor neurons was shown to be a ..
  8. pmc Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model
    Yimin Hua
    Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
    Nature 478:123-6. 2011
    ..There is no effective SMA treatment, but SMN restoration in spinal cord motor neurons is thought to be necessary and sufficient...
  9. ncbi ALS: a disease of motor neurons and their nonneuronal neighbors
    Severine Boillee
    Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California, San Diego, La Jolla, California 92093, USA
    Neuron 52:39-59. 2006
    Amyotrophic lateral sclerosis is a late-onset progressive neurodegenerative disease affecting motor neurons. The etiology of most ALS cases remains unknown, but 2% of instances are due to mutations in Cu/Zn superoxide dismutase (SOD1)...
  10. pmc Conversion of mouse and human fibroblasts into functional spinal motor neurons
    Esther Y Son
    Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    Cell Stem Cell 9:205-18. 2011
    ..expression of select transcription factors is sufficient to convert mouse and human fibroblasts into induced motor neurons (iMNs)...
  11. ncbi Microglia in ALS: the good, the bad, and the resting
    Jenny S Henkel
    Department of Neurology, Methodist Neurological Institute, The Methodist Hospital Research Institute, The Methodist Hospital, 6560 Fannin Street, Houston, TX 77030, USA
    J Neuroimmune Pharmacol 4:389-98. 2009
    ..Thus, the cumulative evidence suggests that inflammation plays a central role in ALS and manipulating these microglial effector functions may potentially modify the outcome of this devastating disease...
  12. pmc Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons
    Makiko Nagai
    Department of Neurology, Columbia University, 710 West 168th Street, New York, New York 10032, USA
    Nat Neurosci 10:615-22. 2007
    ..Here, we show that expression of mutated human SOD1 in primary mouse spinal motor neurons does not provoke motor neuron degeneration...
  13. pmc Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis
    Chi Hong Wu
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nature 488:499-503. 2012
    ..PFN1 mutants also display decreased bound actin levels and can inhibit axon outgrowth. Furthermore, primary motor neurons expressing mutant PFN1 display smaller growth cones with a reduced F/G-actin ratio...
  14. ncbi Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity
    S Arber
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA
    Neuron 23:659-74. 1999
    The homeobox gene Hb9, like its close relative MNR2, is expressed selectively by motor neurons (MNs) in the developing vertebrate CNS...
  15. pmc Targeted depletion of TDP-43 expression in the spinal cord motor neurons leads to the development of amyotrophic lateral sclerosis-like phenotypes in mice
    Lien Szu Wu
    Institute of Molecular Biology, Academia Sinica, Taipei 11574, Taiwan
    J Biol Chem 287:27335-44. 2012
    ..mouse gene targeting approach, we show that mice with inactivation of the Tardbp gene in the spinal cord motor neurons (HB9:Cre-Tardbp(lx/-)) exhibit progressive and male-dominant development of ALS-related phenotypes including ..
  16. pmc Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model
    Francesco Paolo Di Giorgio
    The Stowers Medical Institute, the Harvard Stem Cell Institute Harvard University, 7 Divinity Ave, Cambridge, Massachusetts 02138, USA
    Nat Neurosci 10:608-14. 2007
    ..derived from mice carrying normal or mutant transgenic alleles of the human SOD1 gene were used to generate motor neurons by in vitro differentiation...
  17. ncbi Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice
    A M Clement
    Ludwig Institute for Cancer Research, University of California, 9500 Gilman Drive, La Jolla, CA 92093 0670, USA
    Science 302:113-7. 2003
    ..inherited [correct] form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motor neurons, is caused by dominant mutations in the ubiquitously expressed Cu-Zn superoxide dismutase (SOD1)...
  18. pmc Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice
    Xiu Shan
    Department of Pathology, Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 2196, USA
    Proc Natl Acad Sci U S A 107:16325-30. 2010
    ..However, the function of TDP-43 in motor neurons remains undefined...
  19. pmc Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?
    Arthur H M Burghes
    Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA
    Nat Rev Neurosci 10:597-609. 2009
    ..the survival motor neuron1 gene (SMN1), leading to reduced SMN protein levels and a selective dysfunction of motor neurons. SMN, together with partner proteins, functions in the assembly of small nuclear ribonucleoproteins (snRNPs), ..
  20. pmc Skeletal muscle-restricted expression of human SOD1 causes motor neuron degeneration in transgenic mice
    Margaret Wong
    Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, 558 Ross Building, 720 Rutland Avenue, Baltimore, MD 21205 2196, USA
    Hum Mol Genet 19:2284-302. 2010
    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons (MNs) that causes skeletal muscle paralysis. Familial forms of ALS are linked to mutations in the superoxide dismutase-1 (SOD1) gene...
  21. ncbi Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo
    Paola Arlotta
    MGH HMS Center for Nervous System Repair, Departments of Neurosurgery and Neurology, Program in Neuroscience and Harvard Stem Cell Institute, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
    Neuron 45:207-21. 2005
    ..In order to elucidate molecular mechanisms underlying the specification and development of corticospinal motor neurons (CSMN), we purified CSMN at distinct stages of development in vivo and compared their gene expression to two ..
  22. pmc Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN
    Kevin D Foust
    Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, Columbus, Ohio, USA
    Nat Biotechnol 28:271-4. 2010
    ..demonstrated that self-complementary adeno-associated virus 9 (scAAV9) can infect approximately 60% of motor neurons when injected intravenously into neonatal mice...
  23. pmc SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing
    Zhenxi Zhang
    Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6148, USA
    Cell 133:585-600. 2008
    The survival of motor neurons (SMN) protein is essential for the biogenesis of small nuclear RNA (snRNA)-ribonucleoproteins (snRNPs), the major components of the pre-mRNA splicing machinery...
  24. ncbi Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo
    Edor Kabashi
    Centre of Excellence in Neuromics, Department of Medicine, Universite de Montre al, Montreal, Quebec, Canada
    Hum Mol Genet 19:671-83. 2010
    ..consistently reported TARDBP mutations (A315T, G348C and A382T) were tested in cell lines, primary cultured motor neurons and living zebrafish embryos...
  25. pmc Amyotrophic lateral sclerosis
    Lokesh C Wijesekera
    MRC Centre for Neurodegeneration Research, Department of Clinical Neuroscience, Institute of Psychiatry, Kings College London, London, UK
    Orphanet J Rare Dis 4:3. 2009
    ..The management of ALS is supportive, palliative, and multidisciplinary. Non-invasive ventilation prolongs survival and improves quality of life. Riluzole is the only drug that has been shown to extend survival...
  26. pmc Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice
    Ya Fei Xu
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA
    J Neurosci 30:10851-9. 2010
    ..This TDP-43 transgenic line provides a valuable tool for identifying potential roles of wild-type TDP-43 within the CNS and for studying TDP-43-associated neurotoxicity...
  27. pmc Circuits controlling vertebrate locomotion: moving in a new direction
    Martyn Goulding
    Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Neurosci 10:507-18. 2009
    ....
  28. pmc Motor neuron rescue in spinal muscular atrophy mice demonstrates that sensory-motor defects are a consequence, not a cause, of motor neuron dysfunction
    Rocky G Gogliotti
    Human Molecular Genetics Program, Children s Memorial Research Center, Chicago, Illinois 60614, USA
    J Neurosci 32:3818-29. 2012
    The loss of motor neurons (MNs) is a hallmark of the neuromuscular disease spinal muscular atrophy (SMA); however, it is unclear whether this phenotype autonomously originates within the MN...
  29. ncbi The BMP homolog Gbb provides a retrograde signal that regulates synaptic growth at the Drosophila neuromuscular junction
    Brian D McCabe
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Neuron 39:241-54. 2003
    ..These experiments reveal that a muscle-derived BMP retrograde signal participates in coordinating neuromuscular synapse development and growth...
  30. ncbi Autophagy in spinal cord motor neurons in sporadic amyotrophic lateral sclerosis
    Shoichi Sasaki
    Department of Neurology, Tokyo Women s Medical University, Tokyo, Japan
    J Neuropathol Exp Neurol 70:349-59. 2011
    ..In the ALS cases, the somata of normal-appearing and degenerated motor neurons and round bodies were occasionally immunostained for LC3; round bodies and skein-like inclusions were ..
  31. pmc Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis
    David R Beers
    Department of Neurology, Methodist Neurological Institute, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 103:16021-6. 2006
    ..This study confirms the importance of microglia as a double-edged sword, and focuses on the importance of targeting microglia to minimize cytotoxicity and maximize neuroprotection in neurodegenerative diseases...
  32. ncbi Locomotor circuits in the mammalian spinal cord
    Ole Kiehn
    Mammalian Locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm S17177, Sweden
    Annu Rev Neurosci 29:279-306. 2006
    ..Molecular and genetic approaches that have the potential to elucidate the function of populations of CPG interneurons are also discussed...
  33. pmc Induced pluripotent stem cells from a spinal muscular atrophy patient
    Allison D Ebert
    The Waisman Center, The Stem Cell and Regenerative Medicine Center, University of Wisconsin Madison, 1500 Highland Avenue, Madison, Wisconsin 53705, USA
    Nature 457:277-80. 2009
    ..Patients have selective loss of lower motor neurons resulting in muscle weakness, paralysis and often death...
  34. pmc Astrocytes from familial and sporadic ALS patients are toxic to motor neurons
    Amanda M Haidet-Phillips
    The Research Institute at Nationwide Children s Hospital, Columbus, Ohio, USA
    Nat Biotechnol 29:824-8. 2011
    ..both FALS and SALS patients, we show that astrocytes derived from both patient groups are similarly toxic to motor neurons. We also demonstrate that SOD1 is a viable target for SALS, as its knockdown significantly attenuates ..
  35. pmc Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy
    Tara L Martinez
    Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Neurosci 32:8703-15. 2012
    ..To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN ..
  36. ncbi Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons
    John T Dimos
    Harvard Stem Cell Institute, Stowers Medical Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
    Science 321:1218-21. 2008
    ..These patient-specific iPS cells possess properties of embryonic stem cells and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.
  37. ncbi The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy
    U R Monani
    Departments of Neurology, College of Medicine, Ohio State University, Columbus, OH 43210, USA
    Hum Mol Genet 9:333-9. 2000
    ..We show that Smn (-/-); SMN2 mice carrying one or two copies of the transgene have normal numbers of motor neurons at birth, but vastly reduced numbers by postnatal day 5, and subsequently die...
  38. ncbi TDP-43 is recruited to stress granules in conditions of oxidative insult
    Claudia Colombrita
    Department of Neurology and Laboratory of Neuroscience, Dino Ferrari Center, Università degli Studi di Milano IRCCS Istituto Auxologico Italiano, Milan, Italy
    J Neurochem 111:1051-61. 2009
    ..Although SGs were not evident in ALS brains, we speculate that an altered control of mRNA translation in stressful conditions may trigger motor neuron degeneration at early stages of the disease...
  39. ncbi Transcriptional mechanisms controlling motor neuron diversity and connectivity
    Simon A Dalla Torre di Sanguinetto
    Biozentrum, Department of Cell Biology, University of Basel, Basel, Switzerland
    Curr Opin Neurobiol 18:36-43. 2008
    ..Spinal motor neurons (MNs) provide the trigger to signal the appropriate sequence of muscle contractions and initiate movement...
  40. ncbi Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation
    Francesco Paolo Di Giorgio
    The Harvard Stem Cell Institute, The Stowers Medical Institute, Department of Stem Cell and Regenerative Biology, Cambridge, MA 02138, USA
    Cell Stem Cell 3:637-48. 2008
    ..We show that human spinal motor neurons, but not interneurons, are selectively sensitive to the toxic effect of glial cells carrying an ALS-causing ..
  41. ncbi Mutations in dynein link motor neuron degeneration to defects in retrograde transport
    Majid Hafezparast
    Department of Neurodegenerative Disease, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
    Science 300:808-12. 2003
    Degenerative disorders of motor neurons include a range of progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA)...
  42. ncbi Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior
    Fabian Feiguin
    International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, Italy
    FEBS Lett 583:1586-92. 2009
    ..Our results demonstrate the role of this protein in vivo and suggest an alternative explanation to ALS pathogenesis that may be more due to the lack of TDP 43 function than to the toxicity of the aggregates...
  43. ncbi Motor neuron diversity in development and disease
    Kevin C Kanning
    Department of Pathology, Center for Motor Neuron Biology and Disease, Columbia University Medical Center, New York, NY 10032, USA
    Annu Rev Neurosci 33:409-40. 2010
    Although often considered as a group, spinal motor neurons are highly diverse in terms of their morphology, connectivity, and functional properties and differ significantly in their response to disease...
  44. pmc Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model
    Yimin Hua
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Genes Dev 24:1634-44. 2010
    ..survival of motor neuron 2, centromeric (SMN2) exon 7 inclusion to express more full-length SMN protein in motor neurons is a promising approach to treat spinal muscular atrophy (SMA), a genetic neurodegenerative disease...
  45. ncbi Skeletal muscle is a primary target of SOD1G93A-mediated toxicity
    Gabriella Dobrowolny
    Institute Pasteur Cenci Bolognetti, Department of Histology and Medical Embryology, CE BEMM and IIM, Sapienza University of Rome, Via A Scarpa, 14 Rome 00161, Italy
    Cell Metab 8:425-36. 2008
    ..These data demonstrate that skeletal muscle is a primary target of SOD1(G93A) -mediated toxicity and disclose the molecular mechanism whereby oxidative stress triggers muscle atrophy...
  46. pmc Amyotrophic lateral sclerosis-associated proteins TDP-43 and FUS/TLS function in a common biochemical complex to co-regulate HDAC6 mRNA
    Sang Hwa Kim
    Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
    J Biol Chem 285:34097-105. 2010
    Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that preferentially targets motor neurons. It was recently found that dominant mutations in two related RNA-binding proteins, TDP-43 (43-kDa TAR DNA-binding ..
  47. pmc Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis
    Marcelo R Vargas
    Division of Pharmaceutical Sciences, University of Wisconsin Madison, Madison, Wisconsin 53705 2222, USA
    J Neurosci 28:13574-81. 2008
    ..forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons. Non-neuronal cells, including astrocytes, shape motor neuron survival in ALS and are a potential target to ..
  48. ncbi Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1
    Jeremy S Dasen
    Smilow Neuroscience Program, Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    Cell 134:304-16. 2008
    The precision with which motor neurons innervate target muscles depends on a regulatory network of Hox transcription factors that translates neuronal identity into patterns of connectivity...
  49. ncbi Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression
    Jeffrey D Rothstein
    Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287, USA
    Nature 433:73-7. 2005
    ..Thus these studies provide a class of potential neurotherapeutics that act to modulate the expression of glutamate neurotransmitter transporters via gene activation...
  50. pmc Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis
    Brian C Kraemer
    Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA
    Acta Neuropathol 119:409-19. 2010
    ..strength and display deficits in a standard inverted grid test despite no evidence of pathologic changes in motor neurons. Thus, TDP-43 is essential for viability, and mild reduction in TDP-43 function is sufficient to cause motor ..
  51. ncbi Retrograde BMP signaling controls synaptic growth at the NMJ by regulating trio expression in motor neurons
    Robin W Ball
    Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada
    Neuron 66:536-49. 2010
    ..We further find that Trio is required in motor neurons for normal structural growth...
  52. pmc Deficits in axonal transport precede ALS symptoms in vivo
    Lynsey G Bilsland
    Molecular Neuropathobiology Laboratory, Cancer Research UK London Research Institute, London WC2A 3LY, United Kingdom
    Proc Natl Acad Sci U S A 107:20523-8. 2010
    ..A deficit in axonal transport may therefore be a key pathogenic event in ALS and an early disease indicator of motor neuron degeneration...
  53. pmc TDP-43-mediated neuron loss in vivo requires RNA-binding activity
    Aaron Voigt
    Department of Neurology, University Medical Center, RWTH Aachen, Aachen, Germany
    PLoS ONE 5:e12247. 2010
    ..Using this bi-systemic approach we uncovered a requirement of inherent TDP-43 RNA-binding function--but not ALS/FTLD-linked mutation, mislocalization, or truncation--for TDP-43-mediated neurotoxicity in vivo...
  54. ncbi A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis
    Luis H Barbeito
    Departamento de Neurobiologia Celular y Molecular, Instituto de Investigaciones Biologicas Clemente Estable, Avenida Italia 3318 CP 11600, Montevideo, Uruguay
    Brain Res Brain Res Rev 47:263-74. 2004
    A strong glial reaction typically surrounds the affected upper and lower motor neurons and degenerating descending tracts of ALS patients...
  55. ncbi Robust spinal motor neuron transduction following intrathecal delivery of AAV9 in pigs
    T Federici
    Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA
    Gene Ther 19:852-9. 2012
    ..of the spinal cord, three consecutive boluses via a temporary catheter resulted in diffuse transduction of motor neurons (MNs) throughout the cervical, thoracic and lumbar spinal cords...
  56. ncbi Visualization of cranial motor neurons in live transgenic zebrafish expressing green fluorescent protein under the control of the islet-1 promoter/enhancer
    S Higashijima
    Inheritance and Variation Group, Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Honmachi, Kawaguchi, Saitama 332 0012, Japan
    J Neurosci 20:206-18. 2000
    ..germ line-transmitting transgenic zebrafish that express green fluorescent protein (GFP) in the cranial motor neurons. This was accomplished by fusing GFP sequences to Islet-1 promoter/enhancer sequences that were sufficient for ..
  57. pmc Characterization of the axon initial segment (AIS) of motor neurons and identification of a para-AIS and a juxtapara-AIS, organized by protein 4.1B
    Amandine Duflocq
    INSERM UMRS 952, 9 Quai St Bernard, F 75005, Paris, France
    BMC Biol 9:66. 2011
    ..after the AIS, another question then arises as to how would the axon be organized at its first myelin attachment site; since AISs are different from nodes of Ranvier, would this particular axonal region resemble a hemi-node of Ranvier?..
  58. pmc A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophy
    Matteo Ruggiu
    Department of Pathology and Cell Biology, Columbia University, New York, New York, USA
    Mol Cell Biol 32:126-38. 2012
    ..cell type-specific differences in the efficiency of exon 7 splicing contribute to the vulnerability of SMA motor neurons. We show that normal motor neurons express markedly lower levels of full-length SMN mRNA from SMN2 than do ..
  59. ncbi A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice
    Smita Saxena
    Friedrich Miescher Institut, Novartis Research Foundation, Basel, Switzerland
    Nat Neurosci 12:627-36. 2009
    ..Thus, whereas all motoneurons are preferentially affected in ALS, ER stress responses in specific motoneuron subtypes influence the progressive manifestations of weakening and paralysis...
  60. ncbi Ectopic and increased expression of Fasciclin II alters motoneuron growth cone guidance
    D M Lin
    Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720
    Neuron 13:507-23. 1994
    ..These phenotypes show that changes in the pattern and level of Fas II expression can alter growth cone guidance, apparently in part by modulating the ability of these growth cones to respond to other guidance cues...
  61. pmc Postsymptomatic restoration of SMN rescues the disease phenotype in a mouse model of severe spinal muscular atrophy
    Cathleen M Lutz
    The Jackson Laboratory, Bar Harbor, Maine 04609, USA
    J Clin Invest 121:3029-41. 2011
    ..of opportunity from P4 through P8 defined by the extent of neuromuscular synapse pathology and the ability of motor neurons to respond to SMN induction, following which restoration of the protein to the organism failed to produce ..
  62. ncbi Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS
    Bradley J Turner
    MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK
    Prog Neurobiol 85:94-134. 2008
    ..This review summarises the wealth of known genetic and therapeutic modifiers in rodent models with SOD1 mutations and discusses these in the wider context of ALS pathoetiology and treatment...
  63. ncbi Spinal muscular atrophy: going beyond the motor neuron
    Gillian Hamilton
    Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK
    Trends Mol Med 19:40-50. 2013
    ..Traditionally, reduced levels of SMN were thought to cause the selective death of lower motor neurons, leading to denervation and atrophy of skeletal muscles...
  64. pmc Shared resistance to aging and ALS in neuromuscular junctions of specific muscles
    Gregorio Valdez
    Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts, United States of America
    PLoS ONE 7:e34640. 2012
    ..Of these factors, muscle innervation by brainstem motor neurons correlated best with resistance to age-related decline...
  65. ncbi Spinal inhibitory interneuron pathology follows motor neuron degeneration independent of glial mutant superoxide dismutase 1 expression in SOD1-ALS mice
    Mehdi Hossaini
    Department of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands
    J Neuropathol Exp Neurol 70:662-77. 2011
    ..Ubiquitinated inclusions appeared in interneurons before 20 weeks of age, that is, after their development in motor neurons but before the onset of clinical signs and major motor neuron degeneration, which starts from 25 weeks of age...
  66. pmc Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model
    Gabriella Dobrowolny
    Department of Histology and Medical Embryology, CE BEMM and Interuniversity Institute of Myology, University of Rome La Sapienza, 14 00161 Rome, Italy
    J Cell Biol 168:193-9. 2005
    ..sclerosis (ALS) is a progressive neurodegenerative disease characterized by a selective degeneration of motor neurons, atrophy, and paralysis of skeletal muscle...
  67. pmc Early motor neuron pool identity and muscle nerve trajectory defined by postmitotic restrictions in Nkx6.1 activity
    Natalia V De Marco Garcia
    Howard Hughes Medical Institute, Columbia University Medical Center, New York, NY 10032, USA
    Neuron 57:217-31. 2008
    The fidelity with which spinal motor neurons innervate their limb target muscles helps to coordinate motor behavior, but the mechanisms that determine precise patterns of nerve-muscle connectivity remain obscure...
  68. pmc A yeast functional screen predicts new candidate ALS disease genes
    Julien Couthouis
    Departments of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 108:20881-90. 2011
    ..Immunohistochemistry of postmortem spinal cord tissue revealed mislocalization of TAF15 in motor neurons of patients with ALS...
  69. ncbi Evidence for secretion of Cu,Zn superoxide dismutase via exosomes from a cell model of amyotrophic lateral sclerosis
    Catarina Gomes
    Instituto de Tecnologia Quimica e Biologica, Apartado 127, 2781 901, Oeiras, Portugal
    Neurosci Lett 428:43-6. 2007
    ..SOD1 secretion mediated by exosomes could explain cell-to-cell transfer of mutant toxicity...
  70. ncbi Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals
    Michael A Fox
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Cell 129:179-93. 2007
    ..Thus, multiple target-derived signals permit discrete control of the formation, maturation, and maintenance of presynaptic specializations...
  71. ncbi Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice
    Elisa Dominguez
    UPMC AIM UMR S974, INSERM U 974, CNRS UMR 7215, Institut de Myologie, Universite Pierre et Marie Curie Paris 6, Paris, France
    Hum Mol Genet 20:681-93. 2011
    ..Loss of SMN1 leads to reduced SMN protein levels, inducing degeneration of motor neurons (MN) and progressive muscle weakness and atrophy...
  72. pmc Downregulation of VAPB expression in motor neurons derived from induced pluripotent stem cells of ALS8 patients
    Miguel Mitne-Neto
    University of California San Diego, School of Medicine, Department of Pediatrics Rady Children s Hospital San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, 9500 Gilman Dr, La Jolla, CA 92093, MC 0695, USA
    Hum Mol Genet 20:3642-52. 2011
    ..and their non-carrier siblings were successfully reprogrammed to a pluripotent state and differentiated into motor neurons. We show for the first time that VAPB protein levels are reduced in ALS8-derived motor neurons but, in ..
  73. ncbi Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations
    Heather Flanagan-Steet
    Department of Anatomy and Neurobiology, Washington University Medical School, St Louis, MO 63110, USA
    Development 132:4471-81. 2005
    ..Moreover, many AChR clusters on later-born fast muscle fibers formed at sites that had already been contacted by axons, suggesting heterogeneity in the signaling mechanisms leading to synapse formation by a single axon...
  74. ncbi Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model
    Brian K Kaspar
    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Science 301:839-42. 2003
    ..a progressive, lethal neuromuscular disease that is associated with the degeneration of spinal and brainstem motor neurons, leading to atrophy of limb, axial, and respiratory muscles...
  75. pmc Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding
    Michelle L McWhorter
    Center for Molecular Neurobiology, The Ohio State University, Columbus, OH 43210, USA
    J Cell Biol 162:919-31. 2003
    ..These results show for the first time, in vivo, that Smn functions in motor axon development and suggest that these early developmental defects may lead to subsequent motoneuron loss...
  76. ncbi Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection
    Q Richard Lu
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Cell 109:75-86. 2002
    ..Neither Olig gene is required for astrocytes. These findings, together with fate mapping analysis of Olig-expressing cells, indicate that oligodendrocytes are derived from Olig-specified progenitors that give rise also to neurons...
  77. ncbi Coordinate regulation of motor neuron subtype identity and pan-neuronal properties by the bHLH repressor Olig2
    B G Novitch
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, 701 West 168th Street, New York, NY 10032, USA
    Neuron 31:773-89. 2001
    ..progenitors and has a key role in specifying the subtype identity and pan-neuronal properties of developing motor neurons. The role of Olig2 in the specification of motor neuron subtype identity depends on regulatory interactions ..
  78. ncbi Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis
    Steve Vucic
    Prince of Wales Medical Research Institute, University of New SouthWales, Sydney, NSW 2031, Australia
    Brain 131:1540-50. 2008
    Familial amyotrophic lateral sclerosis (FALS) is an inherited neurodegenerative disorder of the motor neurons. While 10-15% of cases are caused by mutations in the copper/zinc superoxide-dismutase-1 (SOD-1) gene, the dying-forward ..
  79. pmc ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration
    John M Ravits
    Section of Neurology, Virginia Mason Medical Center, Seattle, WA, USA
    Neurology 73:805-11. 2009
    ..This also suggests opportunities for translational research to seek pathobiology directly in the less affected regions of the nervous system...
  80. pmc Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons
    Wilfried Rossoll
    Institute for Clinical Neurobiology, University of Wuerzburg, 97080 Wuerzburg, Germany
    J Cell Biol 163:801-12. 2003
    ..Together, these data suggest that a complex of Smn with its binding partner hnRNP R interacts with beta-actin mRNA and translocates to axons and growth cones of motoneurons...
  81. ncbi Specification of motoneurons from human embryonic stem cells
    Xue Jun Li
    Nat Biotechnol 23:215-21. 2005
    ....
  82. pmc Coordinated actions of the forkhead protein Foxp1 and Hox proteins in the columnar organization of spinal motor neurons
    David L Rousso
    Department of Neurobiology, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Neuron 59:226-40. 2008
    ..that the Forkhead domain transcription factor Foxp1 plays a critical role in defining the columnar identity of motor neurons at each axial position...
  83. pmc A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy
    Umrao R Monani
    Department of Neurology, Ohio State University, Columbus, OH 43210, USA
    J Cell Biol 160:41-52. 2003
    ..Patients lack a functional survival of motor neurons (SMN1) gene, but carry one or more copies of the highly homologous SMN2 gene...
  84. pmc Global control of motor neuron topography mediated by the repressive actions of a single hox gene
    Heekyung Jung
    Howard Hughes Medical Institute, Smilow Neuroscience Program, Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    Neuron 67:781-96. 2010
    ..Genome-wide analysis of Hoxc9 binding suggests that this mode of repression is mediated by direct interactions with Hox regulatory elements, independent of chromatin marks typically associated with repressed Hox genes...
  85. ncbi PKC-1 regulates secretion of neuropeptides
    Derek Sieburth
    Department of Molecular Biology, Simches 7, Massachusetts General Hospital, 185 Cambridge St, Boston, Massachusetts 02114, USA
    Nat Neurosci 10:49-57. 2007
    ..similar to the vertebrate PKC eta and epsilon isoforms, regulates exocytosis of DCVs in Caenorhabditis elegans motor neurons. Mutants lacking PCK-1 activity had delayed paralysis induced by the acetylcholinesterase inhibitor aldicarb, ..
  86. pmc Spinal cholinergic interneurons regulate the excitability of motoneurons during locomotion
    Gareth B Miles
    Department of Anatomy and Neurobiology, Dalhousie University, Halifax, NS, Canada B3H 1X5
    Proc Natl Acad Sci U S A 104:2448-53. 2007
    ..These results highlight a unique component of spinal motor networks that is critical in ensuring that sufficient output is generated by motoneurons to drive motor behavior...
  87. pmc Directed differentiation of human-induced pluripotent stem cells generates active motor neurons
    Saravanan Karumbayaram
    Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
    Stem Cells 27:806-11. 2009
    ..Following methods shown to be effective at generating motor neurons from human embryonic stem cells (hESCs), we found that once specified to a neural lineage, human iPS cells ..
  88. ncbi TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein
    Michael J Strong
    Cell Biology Research Group, Robarts Research Institute, London, Ontario, Canada
    Mol Cell Neurosci 35:320-7. 2007
    The human TAR DNA-binding protein (TDP43) colocalizes with ubiquitinated inclusions in motor neurons in amyotrophic lateral sclerosis (ALS)...
  89. pmc Genetic visualization with an improved GCaMP calcium indicator reveals spatiotemporal activation of the spinal motor neurons in zebrafish
    Akira Muto
    Division of Molecular and Developmental Biology, National Institute of Genetics, Graduate University for Advanced Studies, SOKENDAI, Mishima, Shizuoka 411 8540, Japan
    Proc Natl Acad Sci U S A 108:5425-30. 2011
    ..expressed Gal4FF, a modified version of Gal4, in a subset of spinal neurons including the caudal primary (CaP) motor neurons. We conducted calcium imaging using the SAIGFF213A; UAS:GCaMP-HS double transgenic embryos during the ..
  90. ncbi Neurotrophins are required for nerve growth during development
    K L Tucker
    Department of Neurobiochemistry, Max Planck Institute of Neurobiology, Am Klopferspitz 18a, 82152 Martinsried, Germany
    Nat Neurosci 4:29-37. 2001
    ....
  91. ncbi A Drosophila model of FUS-related neurodegeneration reveals genetic interaction between FUS and TDP-43
    Nicholas A Lanson
    Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
    Hum Mol Genet 20:2510-23. 2011
    Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder characterized by the loss of motor neurons. Fused in sarcoma/translated in liposarcoma (FUS/TLS) and TAR DNA-binding protein (TDP)-43 are DNA/RNA-binding ..
  92. ncbi Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons derived from human embryonic stem cells
    Maria C N Marchetto
    Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Stem Cell 3:649-57. 2008
    ..nature of ALS emerged from the observation that wild-type glial cells extended the survival of SOD1 mutant motor neurons in chimeric mice...
  93. pmc LRP4 serves as a coreceptor of agrin
    Bin Zhang
    Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA
    Neuron 60:285-97. 2008
    ..These observations indicate that LRP4 is a coreceptor of agrin that is necessary for MuSK signaling and AChR clustering and identify a potential target protein whose mutation and/or autoimmunization may cause muscular dystrophies...
  94. pmc Ubiquilin modifies TDP-43 toxicity in a Drosophila model of amyotrophic lateral sclerosis (ALS)
    Keith A Hanson
    Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
    J Biol Chem 285:11068-72. 2010
    ..Expression of wild-type human TDP-43 protein in Drosophila motor neurons led to motor dysfunction and dramatic reduction of life span...
  95. pmc Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise
    Gregorio Valdez
    Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 107:14863-8. 2010
    ..the incidence of pre- and postsynaptic abnormalities in 24-mo-old mice and attenuated age-related loss of motor neurons and turnover of muscle fibers...
  96. ncbi Current hypotheses for the underlying biology of amyotrophic lateral sclerosis
    Jeffrey D Rothstein
    Department of Neurology and Neuroscience, Brain Science Institute, Johns Hopkins University, Baltimore, MD 21287, USA
    Ann Neurol 65:S3-9. 2009
    ..SOD1 gene and other ALS genes develop pathology reminiscent of the disorder, including progressive death of motor neurons, and have provided insight into the pathogenesis of the disease but have consistently failed to predict ..
  97. ncbi Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling
    J Ericson
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA
    Cell 90:169-80. 1997
    Distinct classes of motor neurons and ventral interneurons are generated by the graded signaling activity of Sonic hedgehog (Shh)...
  98. pmc Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy
    Shingo Kariya
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Hum Mol Genet 17:2552-69. 2008
    ..We suggest that SMA might best be described as a NMJ synaptopathy and that one promising means of treating it could involve maintaining function at the NMJ...
  99. ncbi A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification
    Bennett G Novitch
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, 701 West 168th Street, New York, NY 10032, USA
    Neuron 40:81-95. 2003
    ..Moreover, joint exposure of neural progenitors to retinoids and FGFs suffices to induce motor neuron differentiation in a Shh-independent manner...
  100. pmc Extracellular mutant SOD1 induces microglial-mediated motoneuron injury
    Weihua Zhao
    Department of Neurology, Methodist Neurological Institute, The Methodist Research Institute, The Methodist Hospital, Houston, Texas, USA
    Glia 58:231-43. 2010
    ..This link between mSOD1 and innate immunity may offer novel therapeutic targets in ALS...
  101. ncbi Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy
    Lyndsay M Murray
    Centre for Integrative Physiology and Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh Medical School, Edinburgh, UK
    Hum Mol Genet 19:420-33. 2010
    ..organisms have suggested that low levels of Smn protein disrupt prenatal developmental processes in lower motor neurons, influencing neuronal outgrowth, axon branching and neuromuscular connectivity...

Research Grants73

  1. NIH Director's Pioneer Award
    ERICH JARVIS; Fiscal Year: 2009
    ..or several genetic differences that control the connection of forebrain motor learning pathways onto brainstem motor neurons that normally control the production of innate vocalizations1...
  2. Agrin/alpha 3 Na,K-ATPase signaling at the neuromuscular junction
    Martin A Smith; Fiscal Year: 2012
    ..movements such as locomotion, breathing, and swallowing, depend on the rapid transfer of information between motor neurons and the skeletal muscle fibers they innervate that takes place at a specialized contact called the ..
  3. Epigenetic mechanisms relevant to the pathogenesis of ALS
    Neil W Kowall; Fiscal Year: 2013
    ..The specific aims of the study are: 1) To determine the relationship between LSD1 induction in motor neurons and cell death mediated by oxidative stress in vitro;2) To determine the role of LSD1 in the survival of motor ..
  4. Cellular and Animal Models of FUS Mutations in ALS
    Eric J Huang; Fiscal Year: 2013
    ..Our recent data, however, indicated that the spinal motor neurons in patients with P525L mutation show mislocalization of mutant FUS proteins in neuronal cytoplasm with ..
  5. Role of Potent Trophic Factors on Glia and Motor Neurons in ALS
    Brian K Kaspar; Fiscal Year: 2013
    ..We have developed an in vitro based model of ALS that utilizes stem cells directed to motor neurons and ALS containing astrocytes, which recapitulates the disease...
  6. Ca Signaling in Progression of Amyotrophic Lateral Sclerosis in Skeletal Muscle
    Jingsong Zhou; Fiscal Year: 2013
    ..Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder involving degeneration of motor neurons and atrophy of skeletal muscle...
  7. Enhance Production of Functional Recombinant Human Protein C Variant In Mammalian
    Nienwen Chow; Fiscal Year: 2010
    ..Amyotrophic lateral sclerosis (ALS) is a motor neuron disorder characterized by the degeneration and death of motor neurons. Currently there is no cure for ALS. Most ALS cases are sporadic...
  8. The Role of the Terminal Complement Pathway in ALS
    Scott R Barnum; Fiscal Year: 2013
    ..Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neuron disease that leads to degeneration of motor neurons in the cortex, brainstem and spinal cord resulting in progressive paralysis and ultimately death...
  9. High-affinity RNA targets of Survival Motor Neuron Protein
    Ravindra N Singh; Fiscal Year: 2013
    ..applicant): Spinal muscular atrophy (SMA) is a developmental disorder characterized by a progressive loss of motor neurons during early childhood...
  10. Glutathione in mitochondrial dysfunction and disease progression in ALS-models
    Marcelo R Vargas; Fiscal Year: 2011
    ..mitochondrial dysfunction in the toxicity of astrocytes expressing ALS-linked mutant SOD1s toward co-cultured motor neurons;and 3...
  11. Innate Immune Mechanisms of Motor Neuron Injury
    Timothy Vartanian; Fiscal Year: 2010
    ..Selective degeneration of motor neurons occurs in the setting of diverse insults including RNA viruses such as HIV and West Nile, and in heritable ..
  12. Analysis of the tumor suppressor gene Tsc1 in motor neuron patterning
    Onanong Chivatakarn; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Motor neurons (MNs) enable control over locomotion, respiration and autonomic responses, and are profoundly affected by diseases such as spinal muscle atrophy (SMA) and amyotrophic lateral sclerosis (..
  13. ALS therapies and genomics for mutant TDP-43 and TLS/FUS
    Don W Cleveland; Fiscal Year: 2010
    ..sclerosis (ALS) is an adult-onset neurodegenerative disorder in which premature loss of upper and lower motor neurons leads to fatal paralysis with a typical disease course of one to five years...
  14. Effects of nerve demyelination on auditory synaptic functions
    Jun Hee Kim; Fiscal Year: 2012
    ..to genetic mutations or autoimmune disease, as in the case of multiple sclerosis (MS) can result in increased motor neurons fatigue and nerve impulse conduction failure...
  15. The Role of RNA Splicing Factors in Retinal Degeneration
    Michael Farkas; Fiscal Year: 2012
    ..this case, the neurologic disorder spinal muscular atrophy (SMA), which is caused by mutations in the survival motor neurons (SMN) gene...
  16. Noncoding RNA targets of the spinal muscular atrophy protein
    Livio Pellizzoni; Fiscal Year: 2010
    SMA is an autosomal recessive disorder characterized by degeneration of motor neurons in the spinal cord and skeletal muscle atrophy...
  17. Targeted investigation of tissue specific oxidative stress in the etiology of ALS
    Holly Van Remmen; Fiscal Year: 2013
    ..Through targeted expression of Cre recombinase to specific tissues (e.g., motor neurons, skeletal muscle, microglia and astrocytes) in the Gpx4flfl conditional knockout ALS mutant mice, we will ..
  18. Testing Compounds that Increase SMN levels for Efficacy in Mouse Models of SMA
    Elliot J Androphy; Fiscal Year: 2010
    ..1 in 6,000 live births and clinically manifests as progressive muscle weakness due to deterioration of motor neurons. SMA results from insufficient levels of the survival motor neuron (SMN) protein, usually due to homozygous ..
  19. Dysfunction of neurofilaments in disease: an iPS model of Giant Axonal Neuropathy
    BETHANY LESLIE JOHNSON-KERNER; Fiscal Year: 2012
    ..In these patients, degeneration of motor neurons (MNs) leads to progressive paralysis and death by the third decade of life...
  20. The survival of motor neuron protein in axonal mRNA localization
    PAUL GREGORY DONLIN-ASP; Fiscal Year: 2013
    ..SMA is characterized by gradual loss of motor neurons leading to failed innervation of muscles which results in progressive muscle weakness and eventual death due ..
  21. Axonal Transport Deficits during Hereditary Spastic Paraplegia
    GERARDO ANDRES MORFINI; Fiscal Year: 2013
    ..This hallmark clinical symptom of HSP results from progressive dysfunction and degeneration of upper motor neurons in corticospinal tracts and dorsal column fibers...
  22. REACTIVE OXYGEN SPECIES: STRESS AND DAMAGE IN OLD MUSCLE
    Susan V Brooks; Fiscal Year: 2012
    ..the fields of neurobiology and neurology for studies of the timing and interactions among age-related changes motor neurons, muscle fibers, and mitochondria...
  23. Small Oligonucleotides As Therapeutic Agents Of Spinal Muscular Atrophy
    Ravindra N Singh; Fiscal Year: 2012
    ..Most commonly, SMA results from the reduced levels of full-length SMN protein (SMN) in motor neurons and spinal chord due to the loss of functional Survival Motor Neuron (SMN1) alleles...
  24. Molecular mechanism of regulation of mI(CAT) in intestinal smooth muscle cells
    Michael X Zhu; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Acetylcholine is the primary transmitter released by enteric excitatory motor neurons. It plays a central role in the control of motility of the gastrointestinal tract...
  25. Function of the Zinc Finger Protein ZPR1 in neurodegeneration
    LAXMAN DASS GANGWANI; Fiscal Year: 2013
    ..finger protein ZPR1 in the pathogenesis of spinal muscular atrophy (SMA) caused by mutation of the survival motor neurons (SMN1) gene. SMA is characterized by degeneration of the spinal motor neurons...
  26. A Spontaneous Mouse Model of Motor Neuron Disease
    Kevin L Seburn; Fiscal Year: 2011
    ..immunocytochemistry, and electron microscopy to understand the disease progression and pathology in the motor neurons. This information will allow us to accurately correlate the mouse phenotype with related human diseases...
  27. Role of FUS in ALS
    Haining Zhu; Fiscal Year: 2013
    ..The Drosophila model we established showed motor function deficiency when FUS was over-expressed in motor neurons. Interestingly, Gemin3 was also reported to be required for larval motor function in Drosophila...
  28. Peroxynitrite, nitrotyrosine and HSP90 in neuronal death
    ALVARO G ESTEVEZ; Fiscal Year: 2013
    Our long-term goal is to understand how mutations to SOD can increase oxidative stress and cause the death of motor neurons in amyotrophic lateral sclerosis (ALS)...
  29. Using Drosophila as a model to understand TDP-43 function in ALS
    David B Morton; Fiscal Year: 2012
    ..ALS results from the selective loss of motor neurons, which in ALS patients contain cytoplasmic aggregates of proteins...
  30. Role of Stasimon Dysfunction in Spinal Muscular Atrophy
    Livio Pellizzoni; Fiscal Year: 2013
    ..These will include motor neurons (MNs) in the ventral horns of the lumbar spinal cord and proprioceptive neurons located in the dorsal root ..
  31. Role of p62 in Protein Aggregation and Neurodegeneration in ALS
    Haining Zhu; Fiscal Year: 2009
    ..We previously reported that p62 was co-localized with mutant SOD1 in the protein aggregates in spinal motor neurons in G93A SOD1 transgenic mice...
  32. Novel neurotrophic therapy in a mouse model of ALS
    Alpaslan Dedeoglu; Fiscal Year: 2013
    ..lateral sclerosis (ALS) is an enigmatic neurodegenerative disorder characterized by the selective loss of motor neurons that results in rapid progressive motor weakness and early death due to respiratory failure...
  33. FUNCTION OF THE ENTERIC NERVOUS SYSTEM
    JACKIE WOOD; Fiscal Year: 2013
    ..Aim 3. Identification of neurotransmitters released by motor neurons of the ENS at their junctions with neighboring mast cells and to identify the receptor subtypes for the ..
  34. Translating a CSF delivered AAV9-SMN for treatment of Spinal Muscular Atrophy
    Brian K Kaspar; Fiscal Year: 2013
    ..a pre-IND Aim 2: Optimize intrathecal dosing in nonhuman primates for most efficient targeting of spinal motor neurons using scAAV9.CB...
  35. Melanocortin-4 Receptor-dependent regulation of energy balance after gastric bypa
    Vincent Aguirre; Fiscal Year: 2013
    ..of body weight and glucose metabolism (which is dysregulated in diabetes), including the vagus nerve and motor neurons of the sympathetic nervous system (SNS)...
  36. Nemo-Like Kinase and the Pathogenesis of Spinal and Bulbar Muscular Atrophy
    TIFFANY WERLYNE TODD; Fiscal Year: 2013
    ..if there is a genetic interaction between NLK and the mutant AR using both photoreceptor neurons and the motor neurons/neuromuscular junction as model tissues...
  37. Mechanism Underlying Neurodegeneration Caused by Dysfunction of Pre-mRNA Splicing
    Yichang Jia; Fiscal Year: 2012
    ..In addition, I will identify the RNA targets disrupted by expression of the mutant U2 snRNAs in motor neurons, which are primarily affected in several motor neuron diseases potentially caused by misregulation of splicing...
  38. Role of ABC efflux transporters in ALS
    Davide Trotti; Fiscal Year: 2013
    ..sclerosis (ALS) is one of the most devastating and lethal progressive neuromuscular disorders, affecting motor neurons in the spinal cord and motor cortex...
  39. Unconventional Synaptic Modulation at the Vertebrate Neuromuscular Junction
    Clark A Lindgren; Fiscal Year: 2010
    ..Although vertebrate motor neurons have long been known to express high levels of NAAG, the function of this peptide at the NMJ has not been ..
  40. Mechanisms of degeneration in the spinal cord and musculoskeletal system in SMA
    SANIYA FAYZULLINA; Fiscal Year: 2013
    ..because little is known about the function of SMN and the pathobiology of the disease, except that it affects motor neurons (MNs)...
  41. SMN Control of snRNP Biogenesis: Role in RNA Splicing and Motor Neuron Survival
    Livio Pellizzoni; Fiscal Year: 2013
    ..Despite these advances, how defective SMN function in snRNP biogenesis selectively affects motor neurons is unknown...
  42. The Functional Role of RBM45 in Gene Expression and Neurodegeneration
    Mahlon Collins; Fiscal Year: 2013
    ..Pathologically, ALS is characterized by the death of motor neurons of the corticospinal tract, resulting in a numerous debilitating symptoms culminating with paralysis and death...
  43. Development and Functional Analysis of Components of the Zebrafish Serotonin Sign
    Kenneth N Wallace; Fiscal Year: 2012
    ..IPANs synapse with interneurons and motor neurons creating peristaltic and secremotor responses...
  44. Transgenic Study of ALS-Linked CCS Mutations
    Han Xiang Deng; Fiscal Year: 2011
    ..applicant): Amyotrophic lateral sclerosis (ALS) is a progressive paralytic disorder caused by degeneration of motor neurons in the brain and spinal cord. Most ALS cases are sporadic, but approximately 5-10% are familial...
  45. Pre-clinical testing of necrostatin as a potential small molecule for the treatme
    SERGE E PRZEDBORSKI; Fiscal Year: 2012
    ..We and others find that wild-type primary spinal motor neurons (MNs) are selectively killed by mutant SOD1-expressing astrocytes or their conditioned medium by programmed ..
  46. Glutathione in mitochondrial dysfunction and disease progression in ALS-models
    Marcelo R Vargas; Fiscal Year: 2013
    ..mitochondrial dysfunction in the toxicity of astrocytes expressing ALS-linked mutant SOD1s toward co-cultured motor neurons. 3-Aim 3...
  47. Proinflammatory enzymes in amytrophic lateral sclerosis
    SERGE E PRZEDBORSKI; Fiscal Year: 2012
    ..We and others find that mutant SOD1 astrocytes can kill motor neurons. However, mutant astrocytes do not kill spinal interneurons, which are also spared in the spinal cord of ALS ..
  48. Body Composition and Energy Utilization in Spinal Muscular Atrophy
    Douglas Michael Sproule; Fiscal Year: 2012
    ..neuromuscular disease marked by progressive weakness and muscle atrophy resulting from the loss of spinal cord motor neurons. SMA presents across a clinical spectrum, ranging from extremely weak infants with a historically dismal ..
  49. Adeno-associated Viral Vector Modification for Targeted Motor Neuron Therapy
    Nicholas M Boulis; Fiscal Year: 2010
    ..MND), such as Amyotrophic Lateral Sclerosis (ALS), result from death of cells in the nervous system called motor neurons (MN)...
  50. Regulation of SMN and Identification of its Downstream Target
    Judith Jebanathirajah Steen; Fiscal Year: 2013
    ..SMA occurs due to decreased amount of FL-SMN protein in spinal motor neurons. Therefore, much of the effort for therapeutic interventions in SMA has focused on increasing the level of FL-..
  51. MR and BL Tracking of Stem/Progenitor Cells in the CNS
    Jeff W Bulte; Fiscal Year: 2013
    ..and dual luciferase (Luc-BLI)-transducted glial restrictor precursors (GRPs) or embryonic stem cell-derived motor neurons (ESC-MNs) will be transplanted in the spinal cord of rats following the induction of MND disease...
  52. Combined Stem Cell and Anti-Oxidative Therapy for ALS
    Jason R Thonhoff; Fiscal Year: 2010
    ..lateral sclerosis (ALS) is a devastating neurological disease characterized by the selective degeneration of motor neurons in adults...
  53. Therapeutic Development for Amyotrophic Lateral Sclerosis in a Canine Model
    JOAN RIPLEY COATES; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons resulting in stiffness, slowing of movement, and severe muscle wasting and weakness...
  54. Regulation of Sensory-Motor Connectivity by Semaphorin-Plexin Signaling
    Yutaka Yoshida; Fiscal Year: 2013
    ..is expressed by subsets of proprioceptive sensory neurons, while its ligand sema3E is expressed by subsets of motor neurons. We hypothesize that sema-plexin combinations contro l synapse formation and synaptic specificity in the ..
  55. Novel RNAi therapy for ALS and other Neurodegenerative Disorders
    Lyn Libertine; Fiscal Year: 2011
    ..Summary / Abstract Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the central nervous system...
  56. Motor neuron generation from SMA patient-derived induced pluripotent stem cells
    Allison D Ebert; Fiscal Year: 2010
    ..caused by a homozygous loss of the survival motor neuron-1 (SMN) gene leading to the progressive loss of alpha-motor neurons in the spinal cord causing atrophy of trunk and limb muscles...
  57. Local Circuit Properties of Mouse Corticospinal Neurons
    Patrick L Sheets; Fiscal Year: 2011
    ..epilepsy, and movement disorders including amyotrophic lateral sclerosis (ALS), a disease affecting upper motor neurons. Primary motor cortex (M1) is centrally involved in voluntary movement and other aspects of motor control...
  58. Molecular Mechanisms of SOD1-linked ALS (P01)
    Joan Selverstone Valentine; Fiscal Year: 2013
    ..Project 2 (Dr. Martina Wiedau-Pazos) will use stem cell-derived motor neurons and glia and project 3 (Dr...
  59. The Nrf2-ARE Pathway in Amyotrophic Lateral Sclerosis
    Jeffrey A Johnson; Fiscal Year: 2013
    ..We hypothesize that Nrf2-ARE activation and GSH production in the astrocyte will protect motor neurons in models of ALS in vitro and in vivo...
  60. Neural substrates for matching hearing to utterance
    Darcy B Kelley; Fiscal Year: 2012
    ..vocal circuit - receives auditory information and projects directly to the major hindbrain afferent of vocal motor neurons, nucleus DTAM...
  61. The role of Usp 14 in regulating neuronal function
    SCOTT MICHAEL WILSON; Fiscal Year: 2013
    ..atrophy (SMA);however, little is known about the pathways that regulate synaptic activity and development in motor neurons. Although transcriptional mechanisms have been shown to regulate critical steps in the development of the ..
  62. Spinal cord injury: Targeting local inhibition to improve outcome
    Linda J Noble; Fiscal Year: 2010
    ..most likely results in the decreased activity of inhibitory interneurons, which causes overreaction of motor neurons. The primary medications used to treat spasticity either enhance neural inhibition or inhibit muscle ..
  63. Arginase and Regulation of Nitric Oxide Synthase in ALS
    Rajiv Ratan; Fiscal Year: 2004
    ..loss of nerve cells in the anterior horns of the spinal cord, the motor nuclei of the brainstem, and the upper motor neurons of the cerebral cortex...
  64. Cone snail venom peptides that modulate zebrafish spinal motor activity
    Joseph Schulz; Fiscal Year: 2009
    ..A prominent neuroexcitatory peptide in the venom of this species,c4a causes repetitive firing in motor neurons and disrupts rhythmic motor activity that controls swimming in zebrafish (Danio rerio)...
  65. GENETIC CONTROL OF NEUROMUSCULAR DEGENERATION IN MICE
    Gregory Cox; Fiscal Year: 2002
    ..90% of patients) suggest that several different genes are necessary for the normal function and survival of motor neurons. Although some of these genes may be identified in humans, the exploitation of several well-defined mouse ..
  66. Animal models to examine role of ZPR1 protein complexes
    LAXMAN DASS GANGWANI; Fiscal Year: 2010
    ..SMA is caused by mutations of the survival motor neurons (SMN1) gene and characterized by degeneration of spinal motor neurons...
  67. Novel Gene Delivery Development for Spinal Muscular Atrophy
    Brian Kaspar; Fiscal Year: 2009
    ..by applicant): Spinal muscular atrophy (SMA) is a genetic disorder characterized by the loss of lower motor neurons (LMNs) residing along the entire length of the spinal cord...
  68. Intravenous non-viral gene therapy for amyotrophic lateral sclerosis
    Gyula Acsadi; Fiscal Year: 2006
    ..The primary defect in ALS is the degeneration of upper and lower motor neurons causing subsequent muscle weakness and atrophy...
  69. LASER MICROPROBE ANALYSIS OF NEURONAL MERCURY
    Edward Kasarskis; Fiscal Year: 1990
    ..The etiology of amyotrophic lateral sclerosis (ALS), a degenerative disorder characterized by selective death of motor neurons, is unknown...
  70. Retargeting HSV-1 Vectors to Motor Neurons
    Joseph Glorioso; Fiscal Year: 2005
    DESCRIPTION: (provided by applicant) A variety of diseases affect the viability and function of motor neurons located within the spinal cord and projecting to muscle throughout the body...
  71. MOTOR NEURON DEGENERATION IN A MODEL OF ALS
    Erik Pioro; Fiscal Year: 1999
    ..This proposal will examine mechanisms underlying the degenerative changes of spinal cord motor neurons in a genetic mouse model (wobbler) of ALS and their prevention with specific neurotrophic factors...
  72. Potential Contribution of Environmental Metals to ALS
    WILLIAM ATCHISON; Fiscal Year: 2007
    ..disorder which involves decreased skeletal muscle function as a result of loss of upper and/or lower motor neurons. Clinical signs of ALS include skeleta muscle weakness, muscle cramping and fatiguing, slurred speech and ..
  73. GOLGI APPARATUS IN AMYOTROPHIC LATERAL SCLEROSIS
    NICHOLAS GONATAS; Fiscal Year: 2001
    ..Our laboratory was the first to identify the disruption of the GA in a high percentage of motor neurons in ALS and in both asymptomatic and symptomatic transgenic mice expressing the G93A mutation of the human Cu/..