motor neuron disease

Summary

Summary: Diseases characterized by a selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In AMYOTROPHIC LATERAL SCLEROSIS there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes (see MUSCULAR ATROPHY, SPINAL) the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy (BULBAR PALSY, PROGRESSIVE), the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation. (Adams et al., Principles of Neurology, 6th ed, p1089)

Top Publications

  1. 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
  2. ncbi Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease
    Thomas Philips
    VIB Vesalius Research Center, Leuven, Belgium
    Lancet Neurol 10:253-63. 2011
  3. 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
  4. pmc Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS)
    David S Howland
    Department of Molecular Genetics, Wyeth Research, CN8000, Princeton, NJ 08543, USA
    Proc Natl Acad Sci U S A 99:1604-9. 2002
  5. pmc Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders
    Gaia Novarino
    Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA
    Science 343:506-11. 2014
  6. ncbi Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease
    Y Sagot
    Department of Pharmacology, Centre Medical Universitaire, Geneva, Switzerland
    J Neurosci 15:7727-33. 1995
  7. pmc Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease
    Angelo C Lepore
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Nat Neurosci 11:1294-301. 2008
  8. pmc Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS
    Clement Y Chow
    Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
    Am J Hum Genet 84:85-8. 2009
  9. pmc Pedigree with frontotemporal lobar degeneration--motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9
    Agnes A Luty
    Prince of Wales Medical Research Institute, Sydney, NSW, Australia
    BMC Neurol 8:32. 2008
  10. ncbi The epidemiology of motor neuron diseases: a review of recent studies
    P M Worms
    Epidemiology Department, Sanofi-Synthelabo Recherche, 31 Av. P.V. Couturier, 92225, Bagneux, France
    J Neurol Sci 191:3-9. 2001

Detail Information

Publications352 found, 100 shown here

  1. 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
    ..of glycine to alanine at position 93--a change that has little effect on enzyme activity--caused motor neuron disease in transgenic mice...
  2. ncbi Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease
    Thomas Philips
    VIB Vesalius Research Center, Leuven, Belgium
    Lancet Neurol 10:253-63. 2011
    ..An improved understanding of the biological processes that cause neuroinflammation will help to define its medical importance and to identify the therapeutic potential of interfering with this reaction...
  3. 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
    ..These mutations exclusively perturb neuron-specific functions of dynein...
  4. pmc Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS)
    David S Howland
    Department of Molecular Genetics, Wyeth Research, CN8000, Princeton, NJ 08543, USA
    Proc Natl Acad Sci U S A 99:1604-9. 2002
    ..sclerosis (ALS)-linked familial genetic mutation (SOD1(G93A)) in a Sprague-Dawley rat results in ALS-like motor neuron disease. Motor neuron disease in these rats depended on high levels of mutant SOD1 expression, increasing from 8-..
  5. pmc Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders
    Gaia Novarino
    Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA
    Science 343:506-11. 2014
    ..Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease. ..
  6. ncbi Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease
    Y Sagot
    Department of Pharmacology, Centre Medical Universitaire, Geneva, Switzerland
    J Neurosci 15:7727-33. 1995
    ..We examined the effects of Bcl-2 overexpression in a genetic mouse model with motor neuron disease (progressive motor neuronopathy/pmn)...
  7. pmc Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease
    Angelo C Lepore
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Nat Neurosci 11:1294-301. 2008
    ....
  8. pmc Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS
    Clement Y Chow
    Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
    Am J Hum Genet 84:85-8. 2009
    ..Heterozygosity for a deleterious allele of FIG4 appears to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases...
  9. pmc Pedigree with frontotemporal lobar degeneration--motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9
    Agnes A Luty
    Prince of Wales Medical Research Institute, Sydney, NSW, Australia
    BMC Neurol 8:32. 2008
    ..reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND)...
  10. ncbi The epidemiology of motor neuron diseases: a review of recent studies
    P M Worms
    Epidemiology Department, Sanofi-Synthelabo Recherche, 31 Av. P.V. Couturier, 92225, Bagneux, France
    J Neurol Sci 191:3-9. 2001
    ..However, a real increase in the incidence of MNDs, possibly related to environmental factors, cannot be excluded...
  11. ncbi Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study
    Adriano Chio
    Department of Neuroscience, University of Torino, AOU San Giovanni Battista, Via Cherasco 15, 10126 Torino, Italy
    J Neurol Neurosurg Psychiatry 82:740-6. 2011
    ..However, the differential characteristics of these phenotypes are still largely unknown...
  12. pmc Reduced activity of AMP-activated protein kinase protects against genetic models of motor neuron disease
    M A Lim
    Department of Pediatrics, Division of Neurology, Abramson Research Center, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 32:1123-41. 2012
    ..To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C...
  13. ncbi Timelines in the diagnostic evaluation of people with suspected amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)--a 20-year review: can we do better?
    John Douglas Mitchell
    Preston MND Care and Research Centre, Royal Preston Hospital, Sharoe Green Lane, Preston, UK
    Amyotroph Lateral Scler 11:537-41. 2010
    ..Educational interventions among health care professionals both in primary and secondary care may also help shorten diagnostic pathways...
  14. ncbi Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease
    Luc Dupuis
    INSERM, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Strasbourg, F 67085, France
    Exp Neurol 215:146-52. 2009
    ..in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis, the most frequent motor neuron disease in the elderly...
  15. ncbi Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease
    I Le Ber
    CRicm UMRS975 formerly INSERM, UMR_S679, France
    Neurology 72:1669-76. 2009
    Frontotemporal dementia associated with motor neuron disease (FTD-MND) is a rare neurodegenerative disorder that may be inherited by autosomal dominant trait. No major gene has been identified but a locus was mapped on chromosome 9 (9p21...
  16. ncbi Motor neuron disease-associated mutant vesicle-associated membrane protein-associated protein (VAP) B recruits wild-type VAPs into endoplasmic reticulum-derived tubular aggregates
    Eva Teuling
    Department of Neuroscience, Erasmus Medical Center, 3000CA Rotterdam, The Netherlands
    J Neurosci 27:9801-15. 2007
    ..Our data support a model in which reduced levels of VAP family proteins result in decreased ER anchoring of lipid-binding proteins and cause motor neuron degeneration...
  17. ncbi Motor neuron disease occurring in a mutant dynactin mouse model is characterized by defects in vesicular trafficking
    Fiona M Laird
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 28:1997-2005. 2008
    ..disorder characterized by weakness, muscle atrophy, and spasticity, is the most common adult-onset motor neuron disease. Although the majority of ALS cases are sporadic, approximately 5-10% are familial, including those linked ..
  18. ncbi Novel threshold tracking techniques suggest that cortical hyperexcitability is an early feature of motor neuron disease
    Steve Vucic
    Prince of Wales Medical Research Institute and Prince of Wales Clinical School, University of New South Wales, Prince of Wales Hospital, Randwick, Sydney, Australia
    Brain 129:2436-46. 2006
    The dying forward hypothesis of motor neuron disease (MND) suggests that corticomotoneurons induce excitotoxic anterior horn cell death, with involvement of the glutamatergic neurotransmitter system...
  19. ncbi Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse
    Thomas Schmitt-John
    Developmental Biology and Molecular Pathology, Bielefeld University, Germany
    Nat Genet 37:1213-5. 2005
    ..Motoneuron survival and spermiogenesis are severely compromised in the wobbler mouse, indicating that Vps54 has an essential role in these processes...
  20. pmc TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy
    Ann C McKee
    Geriatric Research Education Clinical Center, Bedford Veterans Administration Hospital, Bedford, Massachusetts 01730, USA
    J Neuropathol Exp Neurol 69:918-29. 2010
    ..Three athletes with CTE also developed a progressive motor neuron disease with profound weakness, atrophy, spasticity, and fasciculations several years before death...
  21. ncbi An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria
    P C Wong
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Neuron 14:1105-16. 1995
    ..Four lines of mice accumulating one of these mutant proteins (G37R) develop severe, progressive motor neuron disease. At lower levels of mutant accumulation, pathology is restricted to lower motor neurons, whereas higher ..
  22. ncbi Absence of tumor necrosis factor-alpha does not affect motor neuron disease caused by superoxide dismutase 1 mutations
    Genevieve Gowing
    Laboratory of Molecular Endocrinology, Centre de Recherche du Centre Hospitalier de l Université Laval Research Center, Quebec, Canada G1V 4G2
    J Neurosci 26:11397-402. 2006
    ..Here, we assessed the contribution of TNF-alpha in motor neuron disease in mice overexpressing mutant superoxide dismutase 1 (SOD1) genes linked to familial ALS...
  23. ncbi Overexpression of mutant superoxide dismutase 1 causes a motor axonopathy in the zebrafish
    Robin Lemmens
    Department of Neurology, University Hospital Gasthuisberg, K U Leuven, Belgium
    Hum Mol Genet 16:2359-65. 2007
    ..novel zebrafish model underscores the potential of VEGF for the treatment of ALS and furthermore will permit large-scale genetic and chemical screening to facilitate the identification of new therapeutic targets in motor neuron disease.
  24. ncbi Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading
    Jamuna R Subramaniam
    Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    Nat Neurosci 5:301-7. 2002
    ..in the amount of copper-loaded mutant SOD1, however, it did not modify the onset and progression of motor neuron disease in SOD1-mutant mice...
  25. pmc Messenger RNA oxidation occurs early in disease pathogenesis and promotes motor neuron degeneration in ALS
    Yueming Chang
    Department of Neuroscience, The Ohio State University, Columbus, Ohio, United States of America
    PLoS ONE 3:e2849. 2008
    ..However, previous studies were done in postmortem tissues or cultured neurons. Here, we used transgenic mice to demonstrate the role of RNA oxidation in the process of neurodegeneration...
  26. ncbi Temporal and geographic variation in United States motor neuron disease mortality, 1969-1998
    Curtis W Noonan
    Health Investigations Branch, Division of Health Studies, Agency for Toxic Substances and Disease Registry, Atlanta, GA, USA
    Neurology 64:1215-21. 2005
    To describe temporal trends of motor neuron disease (MND) mortality in the United States...
  27. ncbi Investigation of white matter pathology in ALS and PLS using tract-based spatial statistics
    Olga Ciccarelli
    Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, Queen Square, London
    Hum Brain Mapp 30:615-24. 2009
    ....
  28. ncbi N88S seipin mutant transgenic mice develop features of seipinopathy/BSCL2-related motor neuron disease via endoplasmic reticulum stress
    Takuya Yagi
    Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku ku, Tokyo, Japan
    Hum Mol Genet 20:3831-40. 2011
    ....
  29. ncbi Transforming growth factor-β signaling in motor neuron diseases
    M Katsuno
    Department of Neurology, Nagoya University Graduate School of Medicine, Showa Ku, Nagoya, Japan
    Curr Mol Med 11:48-56. 2011
    ....
  30. pmc Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion
    Jacqueline C Mitchell
    Department of Clinical Neuroscience, Kings College London, King s Centre for Neurodegeneration Research, London SE5 8AF, UK
    Acta Neuropathol 125:273-88. 2013
    ..Furthermore, these mice will provide a new model to study disease mechanism, and test therapies...
  31. ncbi Evidence of multisystem disorder in whole-brain map of pathological TDP-43 in amyotrophic lateral sclerosis
    Felix Geser
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Alzheimer s Disease Core Center, Institute on Aging, Philadelphia, USA
    Arch Neurol 65:636-41. 2008
    ..lateral sclerosis (ALS), and in frontotemporal lobar degeneration with ubiquitinated inclusions, with or without motor neuron disease, but the distribution of TDP-43 pathology in ALS may be more widespread than previously described.
  32. ncbi An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy
    D J MacGowan
    Department of Neurology, Beth Israel Medical Center, New York, NY 10003, USA
    Neurology 57:1094-7. 2001
    ..The patient recovered completely during 1 year after treatment with nelfinavir, zidovudine, and lamivudine, and recovery is sustained nearly 4 years later. Recovery was accompanied by HIV RNA becoming undetectable in plasma and CSF...
  33. pmc Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54
    Peter Green
    Department of Medical and Molecular Genetics, Kings College, London, SE1 9RT, UK
    Am J Hum Genet 86:485-9. 2010
    ..We identified a candidate gene, C20orf54, by studying a consanguineous family with multiple affected individuals and subsequently demonstrated that mutations in this gene were the cause of disease in other, unrelated families...
  34. ncbi Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)
    R G Miller
    Department of Neurology, California Pacific Medical Center, San Francisco, USA
    Amyotroph Lateral Scler Other Motor Neuron Disord 4:191-206. 2003
    ..Riluzole has been approved for treatment of patients with amyotrophic lateral sclerosis in many countries but not all. Questions persist about its clinical utility because of high cost, modest efficacy and concern over adverse effects...
  35. ncbi Quantitative objective markers for upper and lower motor neuron dysfunction in ALS
    H Mitsumoto
    Eleanor and Lou Gehrig MDA ALS Research Center, Columbia University, New York, NY 10032, USA
    Neurology 68:1402-10. 2007
    ..To investigate the value of objective biomarkers for upper (UMN) and lower (LMN) motor neuron involvement in ALS...
  36. ncbi Gene expression analysis of frontotemporal lobar degeneration of the motor neuron disease type with ubiquitinated inclusions
    Manjari Mishra
    Cognitive Neurology and Alzheimer Disease Center, Northwestern University, Feinberg School of Medicine, 320 East Superior St, Chicago, IL, 60611, USA
    Acta Neuropathol 114:81-94. 2007
    ..Our findings point to specific gene-linked-pathways which may be influenced by neurodegenerative disease process and may be targeted for further exploration...
  37. pmc The G59S mutation in p150(glued) causes dysfunction of dynactin in mice
    Chen Lai
    Unit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Neurosci 27:13982-90. 2007
    ..p150(glued), a major component of dynein/dynactin complex, has been linked to an autosomal dominant form of motor neuron disease (MND)...
  38. ncbi Mice lacking cytosolic copper/zinc superoxide dismutase display a distinctive motor axonopathy
    J M Shefner
    Department of Neurology, State University of New York Health Science Center at Syracuse, 13210, USA
    Neurology 53:1239-46. 1999
    ..To characterize the motor neuron dysfunction in two models by performing physiologic and morphometric studies...
  39. pmc hVAPB, the causative gene of a heterogeneous group of motor neuron diseases in humans, is functionally interchangeable with its Drosophila homologue DVAP-33A at the neuromuscular junction
    Andrea Chai
    Center for Neuroscience Research, Royal Dick School of Veterinary Studies, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK
    Hum Mol Genet 17:266-80. 2008
    ..These findings pinpoint to a possible role of hVAPB in synaptic homeostasis and emphasize the relevance of our fly model in elucidating the patho-physiology underlying motor neuron degeneration in humans...
  40. pmc Diagnosis and management of motor neurone disease
    Christopher J McDermott
    Sheffield Care and Research Centre for Motor Neurone Disorders Academic Neurology Unit, Section of Neuroscience, University of Sheffield, Sheffield S10 2RX
    BMJ 336:658-62. 2008
  41. ncbi Astrocyte function and role in motor neuron disease: a future therapeutic target?
    Daniel Blackburn
    Academic Neurology Unit, Sheffield Care and Research Centre for Motor Neuron Disorders, University of Sheffield, Sheffield, United Kingdom
    Glia 57:1251-64. 2009
    ..The review also highlights recent developments indicating the role of astrocytes in motor neuron disease (MND), emphasizing their potential as therapeutic targets and agents in cell replacement therapy...
  42. ncbi Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease
    Agnes A Luty
    Neuroscience Research Australia, Randwick, Sydney, New South Wales, Australia
    Ann Neurol 68:639-49. 2010
    ..Pathological ubiquitinated inclusion bodies observed in FTLD and motor neuron disease (MND) comprise trans-activating response element (TAR) DNA binding protein (TDP-43) and/or fused in sarcoma ..
  43. ncbi Upper and extra-motoneuron involvement in early motoneuron disease: a diffusion tensor imaging study
    Maaike M van der Graaff
    Academic Medical Centre, Department of Neurology room H2 234, PO Box 22660, 1100 DD Amsterdam, The Netherlands
    Brain 134:1211-28. 2011
    ..Voxel-based analyses may be particularly valuable in the evaluation of motor and extra-motor white matter involvement in the early symptomatic stages of motoneuron disease, and for monitoring the spread of pathology over time...
  44. ncbi Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation
    Svitlana Garbuzova-Davis
    Center of Excellence for Aging and Brain Repair and Department of Neurosurgery, University of South Florida, College of Medicine, Tampa, FL 33612, USA
    J Hematother Stem Cell Res 12:255-70. 2003
    ..Most likely, cord blood efficacy is partially due to neuroprotection by modulation of the autoimmune process...
  45. pmc Beta-band intermuscular coherence: a novel biomarker of upper motor neuron dysfunction in motor neuron disease
    Karen M Fisher
    Institute of Neuroscience, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK
    Brain 135:2849-64. 2012
    In motor neuron disease, the focus of therapy is to prevent or slow neuronal degeneration with neuroprotective pharmacological agents; early diagnosis and treatment are thus essential...
  46. ncbi Role of complement in motor neuron disease: animal models and therapeutic potential of complement inhibitors
    Trent M Woodruff
    School of Biomedical Sciences, University of Queensland, St Lucia, QLD 4072, Australia
    Adv Exp Med Biol 632:143-58. 2008
    Amyotrophic lateral sclerosis (ALS) is one of the major forms of motor neuron disease (MND), a group of degenerative disorders causing progressive motor neuron death leading to eventual paralysis and death...
  47. ncbi Effects of cardiotrophin-1 (CT-1) in a mouse motor neuron disease
    H Mitsumoto
    Department of Neurology and Neurosciences, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Muscle Nerve 24:769-77. 2001
    ..01). We conclude that CT-1 exerts myotrophic effects as well as neurotrophic effects in a mouse model of spontaneous MND, a finding that has potential therapeutic implications for human MND...
  48. ncbi Release of [3H]D-aspartate induced by K+-stimulation is increased in the cervical spinal cord of the wobbler mouse: a model of motor neuron disease
    Giambattista Bonanno
    Department of Experimental Medicine, Section of Pharmacology and Toxicology, University of Genova, Viale Cembrano 4, 16148 Genova, Italy
    Neurochem Int 55:302-6. 2009
    ....
  49. ncbi scAAV9 intracisternal delivery results in efficient gene transfer to the central nervous system of a feline model of motor neuron disease
    Thomas Bucher
    INSERM UMR1089, Institut de Recherche Thérapeutique 1, Universite de Nantes, 44007 Nantes Cedex 01, France
    Hum Gene Ther 24:670-82. 2013
    ..vegf) were administered in a limb-expression 1 (LIX1)-deficient cat-a large animal model of lower motor neuron disease-using three different delivery routes to the central nervous system. AAV...
  50. ncbi Evidence for chronic mitochondrial impairment in the cervical spinal cord of a murine model of motor neuron disease
    Barbara Santoro
    Department of Cellular and Molecular Physiological and Pharmacological Sciences, University of Pavia, PV, Italy
    Neurobiol Dis 17:349-57. 2004
    ..Thus, chronic mitochondrial dysfunction has a contributory role in motor neuron degeneration in the wobbler disease...
  51. pmc Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease
    Janel O Johnson
    Laboratory of Neurogenetics, National Institute on Ageing, National Institutes of Health, Bethesda, MD 20892, USA
    Brain 135:2875-82. 2012
    ..Clearly, this makes an excellent candidate therapy for the SLC52A2 mutation-positive patients identified here. Initial riboflavin treatment of one of these patients shows promising results...
  52. ncbi Exposure to environmental toxins and the risk of sporadic motor neuron disease: an expanded Australian case-control study
    R Pamphlett
    The Stacey Motor Neuron Disease Laboratory, Department of Pathology, The University of Sydney, Sydney, NSW, Australia
    Eur J Neurol 19:1343-8. 2012
    It remains unclear what role environmental toxins play in sporadic motor neuron disease (SMND) and its most common subtype, amyotrophic lateral sclerosis (SALS)...
  53. ncbi Aberrant deltaPKC activation in the spinal cord of Wobbler mouse: a model of motor neuron disease
    Kunjan R Dave
    Department of Neurology, University of Miami School of Medicine, Miami, FL 33101, USA
    Neurobiol Dis 18:126-33. 2005
    ..the present study was to define whether deltaPKC activation occurs in Wobbler mouse spinal cord (a model of motor neuron disease)...
  54. pmc Ablation of proliferating cells in the CNS exacerbates motor neuron disease caused by mutant superoxide dismutase
    Jean Nicolas Audet
    Research Centre of CHUQ, Department of Psychiatry and Neurosciences, Laval University, Quebec, Canada
    PLoS ONE 7:e34932. 2012
    ..Here, to investigate the role of proliferating cells in motor neuron disease, SOD1(G93A) transgenic mice were treated intracerebroventicularly (i.c.v...
  55. ncbi A systematic review of behavioural changes in motor neuron disease
    Joost Raaphorst
    Department of Neurology, Academic Medical Centre, University of Amsterdam, The Netherlands
    Amyotroph Lateral Scler 13:493-501. 2012
    b>Motor neuron disease (MND) and the behavioural variant of frontotemporal dementia (bvFTD) are thought to be part of a disease spectrum...
  56. ncbi Retardation of fast axonal transport in wobbler mice
    H Mitsumoto
    Department of Neurology, Cleveland Clinic Foundation, OH 44195
    Muscle Nerve 16:542-7. 1993
    To investigate axonal function in a model of early motor neuron disease, we examined fast and slow components of anterograde axonal transport in the less-affected hindlimb motor neurons of wobbler mice...
  57. pmc Development of a patient reported outcome measure for fatigue in motor neurone disease: the Neurological Fatigue Index (NFI-MND)
    Chris J Gibbons
    Walton Centre for Neurology and Neurosurgery, Lower Lane, Liverpool, UK
    Health Qual Life Outcomes 9:101. 2011
    ..Fatigue was defined as reversible motor weakness and whole-body tiredness that was predominantly brought on by muscular exertion and was partially relieved by rest...
  58. ncbi Primary lateral sclerosis: upper-motor-predominant amyotrophic lateral sclerosis with frontotemporal lobar degeneration--immunohistochemical and biochemical analyses of TDP-43
    Takayuki Kosaka
    Department of Pathology, Brain Research Institute, University of Niigata Department of Neurology, Nishi Niigata Chuo National Hospital, Niigata, Japan
    Neuropathology 32:373-84. 2012
    ..PLS, with 43-kDa TAR DNA-binding protein (TDP-43) abnormality, we examined two adult patients with motor neuron disease, which clinically was limited almost entirely to the UMN system, and was followed by progressive ..
  59. ncbi Predictors of quality of life in carers for people with a progressive neurological illness: a longitudinal study
    Elodie J O'Connor
    School of Psychology, Deakin University, 221 Burwood Highway, Melbourne, Burwood, VIC 3125, Australia
    Qual Life Res 20:703-11. 2011
    ....
  60. pmc Motor neuron disease clinically limited to the lower motor neuron is a diffuse TDP-43 proteinopathy
    Felix Geser
    Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Alzheimer s Disease Core Center, Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 4283, USA
    Acta Neuropathol 121:509-17. 2011
    b>Motor neuron disease (MND) may present as an isolated lower motor neuron (LMN) disorder...
  61. ncbi An epidemiological study of motor neuron disease in Hong Kong
    G C Y Fong
    Department of Medicine, Queen Mary Hospital, Hong Kong
    Amyotroph Lateral Scler Other Motor Neuron Disord 6:164-8. 2005
    Worldwide, the incidence of motor neuron disease (MND) has been increasing steadily over recent decades. We reported a follow-up epidemiology study of MND in this locality...
  62. pmc Stem cell transplantation for motor neuron disease: current approaches and future perspectives
    Genevieve Gowing
    Regenerative Medicine Institute, Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
    Neurotherapeutics 8:591-606. 2011
    ..and questions remain, the beneficial effects observed following transplantation therapy in animal models of motor neuron disease has sparked hope and a number of clinical trials...
  63. ncbi Intracerebroventricular administration of human umbilical cord blood cells delays disease progression in two murine models of motor neuron degeneration
    P Bigini
    Mario Negri Institute for Pharmacological Research, Milan, Italy
    Rejuvenation Res 14:623-39. 2011
    ..In particular, we show that HuCB-MNCs release a series of cytokines and chemokines with antiinflammatory properties that could be responsible of the functional improvement of mouse models of motor neuron degenerative disorders...
  64. pmc Mills' and other isolated upper motor neurone syndromes: in vivo study with 11C-(R)-PK11195 PET
    M R Turner
    Department of Neurology, Institute of Psychiatry, King s College London, UK
    J Neurol Neurosurg Psychiatry 76:871-4. 2005
    ..We conclude that Mills' syndrome is a purely clinical description that should be reserved for patients with a progressive spastic hemiparesis for which no other explanation can be found...
  65. ncbi Hyperbaric oxygen therapy protects against mitochondrial dysfunction and delays onset of motor neuron disease in Wobbler mice
    K R Dave
    Department of Neurology, D4 5, University of Miami School of Medicine, P O Box 016960, Miami, FL 33101, USA
    Neuroscience 120:113-20. 2003
    The Wobbler mouse is a model of human motor neuron disease. Recently we reported the impairment of mitochondrial complex IV in Wobbler mouse CNS, including motor cortex and spinal cord...
  66. ncbi Ventilation in motor neuron disease: difficult decisions in difficult circumstances
    David Oliver
    Wisdom Hospice, High Bank, Rochester, Kent ME1 2NU, UK
    Amyotroph Lateral Scler Other Motor Neuron Disord 5:6-8. 2004
    ..The need for careful forward planning and discussion is emphasised so that decisions can be made after careful consideration and not in an emergency situation...
  67. ncbi Correlates of Quality of Life in people with motor neuron disease (MND)
    L H Goldstein
    Department of Psychology, Institute of Psychiatry, King s College London, PO 77, The Henry Wellcome Building, De Crespigny Park, London SE5 8AF, UK
    Amyotroph Lateral Scler Other Motor Neuron Disord 3:123-9. 2002
    ..questionnaire measures of quality of life (QoL) and physical strength/functional ability in people with motor neuron disease (MND)...
  68. ncbi The relationship between extramotor ubiquitin-immunoreactive neuronal inclusions and dementia in motor neuron disease
    Ian R A Mackenzie
    Department of Pathology, University of British Columbia, Vancouver General Hospital, 855 West 12th Avenue, Canada V5Z 1M9
    Acta Neuropathol 105:98-102. 2003
    Dementia is thought to be an uncommon complication of motor neuron disease (MND)...
  69. ncbi Compound heterozygosity with two novel mutations in the HEXB gene produces adult Sandhoff disease presenting as a motor neuron disease phenotype
    Toshihiro Yoshizawa
    Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, 1 1 1 Tennodai, 305 8575, Tsukuba, Japan
    J Neurol Sci 195:129-38. 2002
    Little information is available on molecular defects involved in adult Sandhoff disease presenting as motor neuron disease phenotype...
  70. ncbi Cognitive dysfunction in lower motor neuron disease: executive and memory deficits in progressive muscular atrophy
    Joost Raaphorst
    Department of Neurology H2 235, Academic Medical Centre, Amsterdam, The Netherlands
    J Neurol Neurosurg Psychiatry 82:170-5. 2011
    ..sclerosis (ALS), cognitive impairments have as yet not been shown in the lower motor neuron variant of motor neuron disease, progressive spinal muscular atrophy (PMA)...
  71. ncbi Neurotoxocariasis associated with lower motor neuron disease. Report of one case
    Josef Finsterer
    Neurological Department, Krankenanstalt Rudolfstiftung, Vienna, Austria
    Rev Med Chil 138:483-6. 2010
    ..Whether lower motor neuron disease was causally related to neurotoxocariasis or due to a general metabolic defect, remains speculative.
  72. ncbi Association between survivor motor neuron 2 (SMN2) gene homozygous deletion and sporadic lower motor neuron disease in a Korean population
    Juwon Kim
    Dept of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
    Ann Clin Lab Sci 40:368-74. 2010
    ..such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) suggest that sporadic lower motor neuron disease (LMND) may be related to SMN gene deletion...
  73. ncbi How does current care practice influence the experience of a new diagnosis of motor neuron disease? A qualitative study of current guidelines-based practice
    Heino Hugel
    Marie Curie Palliative Care Institute, Liverpool, UK
    Amyotroph Lateral Scler 7:161-6. 2006
    ....
  74. ncbi Frontotemporal lobar degeneration with motor neuron disease: a clinical and pathological spectrum
    Christopher M Clark
    Arch Neurol 63:489-90. 2006
  75. ncbi What wires together dies together: verbs, actions and neurodegeneration in motor neuron disease
    Thomas H Bak
    Human Cognitive Neuroscience, Department of Psychology, Edinburgh, UK
    Cortex 48:936-44. 2012
    For more than a century the research on Motor Neuron Disease (MND) has been dominated by a tension between the concept of a selective, purely motor degeneration and a growing realisation of the high frequency and importance of cognitive ..
  76. ncbi Progesterone neuroprotection in the Wobbler mouse, a genetic model of spinal cord motor neuron disease
    Maria Claudia Gonzalez Deniselle
    Instituto de Biologia y Medicina Experimental, Departamento de Bioquimica Humana, Facultad de Medicina, Universidad de Buenos Aires, 1428, Buenos Aires, Argentina
    Neurobiol Dis 11:457-68. 2002
    ..However, because the gene mutation in Wobbler mice is still unknown, further studies are needed to unveil the action of PROG and the mechanism of neuronal death in this genetic model of neurodegeneration...
  77. ncbi Evaluation of occupational exposure to magnetic fields and motor neuron disease mortality in a population-based cohort
    Lauren E Parlett
    Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
    J Occup Environ Med 53:1447-51. 2011
    ..the association between electromagnetic fields and amyotrophic lateral sclerosis, the most common form of motor neuron disease (MND), has been inconclusive...
  78. ncbi Multifocal motor neuropathy: the diagnostic spectrum and response to treatment
    Mark Slee
    Department of Clinical Neurology, University of Oxford, West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK
    Neurology 69:1680-7. 2007
    ..We also test two neurophysiologic criteria for conduction block (CB) for relevance to treatment responsiveness...
  79. ncbi New findings and symptomatic treatment for neurolathyrism, a motor neuron disease occurring in north west Bangladesh
    A Haque
    Department of Neurology, Institute of Postgraduate Medicine and Research, Dhaka, Bangladesh
    Paraplegia 32:193-5. 1994
    ..Sporadic occurrence of HTLV-1 infection (0.9%) and of osteolathyrism was found among the neurolathyrism patients. Osteolathyrism is linked to the consumption of the green shoots of Lathyrus sativus...
  80. ncbi Homozygous exon 7 deletion of the SMN centromeric gene (SMN2): a potential susceptibility factor for adult-onset lower motor neuron disease
    Andoni Echaniz-Laguna
    Service des Maladies du Système Nerveux et du Muscle, Clinique Neurologique, Hĵpital Civil de Strasbourg, France
    J Neurol 249:290-3. 2002
    Mutations in the telomeric copy of the SMN gene (SMN1) are responsible for almost all infantile motor neuron disease (MND). In contrast, the role of the centromeric copy of the SMN gene (SMN2) in MND remains unclear...
  81. ncbi Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy
    M Sendtner
    Department of Neurochemistry, Max Planck Institute for Psychiatry, Martinsried, Germany
    Nature 358:502-4. 1992
    ..The protective and restorative effects of CNTF in this mouse mutant give new perspectives for the treatment of human degenerative motor neuron diseases with CNTF...
  82. ncbi An evaluation of neurophysiological criteria used in the diagnosis of motor neuron disease
    C P Douglass
    Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK
    J Neurol Neurosurg Psychiatry 81:646-9. 2010
    New criteria for the neurophysiological diagnosis of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) were recently proposed at an international symposium in Awaji-shima, Japan...
  83. ncbi Role of neurofilament aggregation in motor neuron disease
    Hong Lin
    Division of Neuropathology, University of Pennsylvania Medical School, Philadelphia, PA 19104 6100, USA
    Ann Neurol 60:399-406. 2006
    A major question in the pathogenesis of motor neuron disease is why motor neurons are selectively susceptible to mutations in widely expressed gene products...
  84. pmc Expression of AMPA and NMDA receptor subunits in the cervical spinal cord of wobbler mice
    Paolo Bigini
    Laboratory of Receptor Pharmacology, Department of Biochemistry and Molecular Pharmacology, Mario Negri Institute for Pharmacological Research, Milano, Italy
    BMC Neurosci 7:71. 2006
    ..Cervical regions from early or late symptomatic wobbler mice (4 or 12 weeks of age) were compared to lumbar tracts (unaffected) and to those of healthy mice...
  85. ncbi Neuroprotective effect of cholinergic differentiation factor/leukemia inhibitory factor on wobbler murine motor neuron disease
    K Ikeda
    Fourth Department of Internal Medicine, Toho University Ohashi Hospital, Tokyo, Japan
    Muscle Nerve 18:1344-7. 1995
  86. ncbi Cancer in patients with motor neuron disease, multiple sclerosis and Parkinson's disease: record linkage studies
    Alessandro F Fois
    Unit of Health Care Epidemiology, Department of Public Health, University of Oxford, Old Road Campus, Old Road, Oxford, UK
    J Neurol Neurosurg Psychiatry 81:215-21. 2010
    To determine the risk of cancer before and after the diagnosis of motor neuron disease (MND), multiple sclerosis (MS) and Parkinson's disease (PD).
  87. ncbi Review: neuromuscular synaptic vulnerability in motor neurone disease: amyotrophic lateral sclerosis and spinal muscular atrophy
    L M Murray
    Centre for Integrative Physiology, University of Edinburgh Medical School, Edinburgh, EH8 9XD, UK
    Neuropathol Appl Neurobiol 36:133-56. 2010
    ..We conclude that future experiments developing therapeutic approaches specifically targeting neuromuscular synaptic vulnerability are likely to be required to prevent or delay disease onset and progression in human MND patients...
  88. pmc Human neural stem cell grafts in the spinal cord of SOD1 transgenic rats: differentiation and structural integration into the segmental motor circuitry
    Leyan Xu
    Department of Pathology, Division of Neuropathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA
    J Comp Neurol 514:297-309. 2009
    ..We have recently shown that human neural stem cell (NSC) grafts ameliorate motor neuron disease in SOD1 transgenic rodents...
  89. ncbi Neural progenitor cells enhance the survival and axonal regeneration of injured motoneurons after transplantation into the avulsed ventral horn of adult rats
    Huanxing Su
    Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
    J Neurotrauma 26:67-80. 2009
    ..Such beneficial effects are possibly due to their inherent ability to secrete various trophic factors after transplantation in vivo...
  90. ncbi Multifocal motor neuropathy with and without conduction block: a single entity?
    E Delmont
    Department of Neurology, University Hospital Pasteur, Nice, France
    Neurology 67:592-6. 2006
    ..To assess if multifocal motor neuropathy (MMN) with and MMN without conduction block (CB) are similar or distinct diseases...
  91. ncbi Multifocal motor neuropathy
    Jan Thies H van Asseldonk
    Department of Clinical Neurophysiology, Neuromuscular Research Group, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Netherlands
    Lancet Neurol 4:309-19. 2005
    ....
  92. ncbi Motor neuron disease: systematic reviews of treatment for ALS and SMA
    Richard W Orrell
    Institute of Neurology, University College London, Rowland Hill Street, London, UK
    Br Med Bull 93:145-59. 2010
    ..Nevertheless, there is an increasing volume of published studies. This review assesses the current evidence for treatment of these conditions...
  93. ncbi Triple-stimulation technique in multifocal neuropathy with conduction block
    Nicolas Deroide
    Department of Neurology and Neuromuscular Diseases, CHU La Timone, 264 rue Saint Pierre, 13385 Marseilles, France
    Muscle Nerve 35:632-6. 2007
    ..Thus, the TST is a useful means for detection of proximal CB and gives NCS considerable additional diagnostic power...
  94. ncbi Clinical entity of frontotemporal dementia with motor neuron disease
    Yoshio Mitsuyama
    Psychogeriatric Center of Daigo Hospital, Miyazaki, Japan
    Neuropathology 29:649-54. 2009
    ..FTLD-TDP, but not Pick's disease with Pick bodies, is often associated with motor neuron disease (MND)...
  95. ncbi Spinocerebellar ataxia type 2 with Levodopa-responsive parkinsonism culminating in motor neuron disease
    Jon Infante
    Service of Neurology, University Hospital Marqués de Valdecilla University of Cantabria, Santander, Spain
    Mov Disord 19:848-52. 2004
    ..We conclude that motor neuron symptoms and signs may be a striking manifestation in SCA2, masking pre-existing cerebellar and extrapyramidal semeiology...
  96. ncbi A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease
    M K Lee
    Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
    Neuron 13:975-88. 1994
    ..Thus, neurofilament mutations can cause selective motor neuron death, and neurofilamentous abnormalities may be a common toxic intermediate that significantly contributes to the motor neuron death in human disease...
  97. ncbi Assessment of disease progression in motor neuron disease
    Jennica M C Winhammar
    Department of Neurology and Multidisciplinary Motor Neurone Disease Clinic, Royal North Shore Hospital, NSW, Australia
    Lancet Neurol 4:229-38. 2005
    b>Motor neuron disease (MND) is characterised by progressive deterioration of the corticospinal tract, brainstem, and anterior horn cells of the spinal cord...
  98. ncbi Dynein: An ancient motor protein involved in multiple modes of transport
    Richard B Vallee
    Departments of Pathology and Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, New York, New York 10032, USA
    J Neurobiol 58:189-200. 2004
    ..The current status of the complex dynein cargo-binding mechanism is evaluated. Finally, recent genetic evidence supporting a role in axonal transport and revealing a role in neurodegenerative conditions is reviewed...
  99. ncbi Wobbler mice modeling motor neuron disease display elevated transactive response DNA binding protein
    J S Dennis
    Laboratory of Molecular Biology, Building 22, Room 123, Research and Development 151, Bay Pines VA Healthcare System, 10000 Bay Pines Boulevard, Bay Pines, FL 33744, USA
    Neuroscience 158:745-50. 2009
    Wobbler mice model motor neuron disease with a substantial decline in motor neurons. TDP-43 is a nucleic acid binding protein that accumulates, along with ubiquitin, in the cytoplasm of amyotrophic lateral sclerosis (ALS) motor neurons...
  100. ncbi Immunohistochemical identification of messenger RNA-related proteins in basophilic inclusions of adult-onset atypical motor neuron disease
    Kengo Fujita
    Department of Neurology, Kansai Medical University, 10 15, Fumizono cho, Moriguchi, Osaka 570 8507, Japan
    Acta Neuropathol 116:439-45. 2008
    ..on RNA-related proteins in the basophilic inclusions (BIs) from patients with adult-onset atypical motor neuron disease. Formalin-fixed, paraffin-embedded sections of the motor cortex and the lumbar spinal cord were examined...
  101. ncbi Riluzole slows the progression of neuromuscular dysfunction in the wobbler mouse motor neuron disease
    Takeo Ishiyama
    Sumitomo Pharmaceuticals Research Division, 1 98 Kasugadenaka 3 chome, Konohanaku, Osaka 554 0022, Japan
    Brain Res 1019:226-36. 2004
    In the wobbler mouse motor neuron disease (MND), we firstly evaluated the effect of riluzole, the only approved drug for amyotrophic lateral sclerosis, and compared it with that of brain-derived neurotrophic factor (BDNF)...

Research Grants72

  1. Genetics of the Neuromuscular Junction: Mechanisms and Disease Models
    Robert W Burgess; Fiscal Year: 2013
    ..This model proposes that altered interaction between GARS and DAXX, a protein implicated in other motor neuron disease pathways, may underlie CMT2D...
  2. Role of Potent Trophic Factors on Glia and Motor Neurons in ALS
    Brian K Kaspar; Fiscal Year: 2013
    Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease, which results in muscle paralysis and ultimate respiratory failure and death. The underlying cause for ALS remains unknown with no cure...
  3. The Role of the Terminal Complement Pathway in ALS
    Scott R Barnum; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): 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 ..
  4. Glutathione in mitochondrial dysfunction and disease progression in ALS-models
    Marcelo R Vargas; Fiscal Year: 2011
    ..provided by applicant): ALS, commonly known as Lou Gehrig's disease, is the most common adult motor neuron disease. The disease's primary hallmark is the selective dysfunction and death of the neurons in the motor ..
  5. Innate Immune Mechanisms of Motor Neuron Injury
    Timothy Vartanian; Fiscal Year: 2010
    ..is to define the function of TLR3 as a potential mediator of motor neuron death in translational models of motor neuron disease. Our hypothesis is that activation of the TLR3 pathway induces selective death in motor neurons as a ..
  6. Food(cassava) cyanogen exposure and motor neuron degeneration
    DANIEL DESIRE TSHALA KATUMBAY; Fiscal Year: 2010
    b>Motor neuron disease is an umbrella term frequently used to designate diseases, especially neurodegenerative conditions that prominently strike the motor system in a fashion that has remained enigmatic...
  7. ALS therapies and genomics for mutant TDP-43 and TLS/FUS
    Don W Cleveland; Fiscal Year: 2010
    ..HEALTH RELEVANCE: Over the last 14 months, a paradigm shift in understanding what goes wrong in the fatal motor neuron disease Amyotrophic Lateral Sclerosis has been initiated by the discoveries that mutations in a pair of RNA binding ..
  8. Noncoding RNA targets of the spinal muscular atrophy protein
    Livio Pellizzoni; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: Spinal muscular atrophy (SMA) is a devastating motor neuron disease caused by decreased levels of the SMN protein...
  9. A Spontaneous Mouse Model of Motor Neuron Disease
    Kevin L Seburn; Fiscal Year: 2011
    ..provided by applicant): The goal of this proposal is to characterize a new spontaneous mouse model of motor neuron disease and identify the causative mutation...
  10. Using Drosophila as a model to understand TDP-43 function in ALS
    David B Morton; Fiscal Year: 2012
    ..intriguing because mutations in the human orthologue of sws, named neuropathy target esterase, lead to motor neuron disease. In addition to testing our hypothesis that the toxic effects of over-expressed TDP-43 result from an ..
  11. Peroxynitrite, nitrotyrosine and HSP90 in neuronal death
    ALVARO G ESTEVEZ; Fiscal Year: 2013
    ..degeneration of motor neurons in ALS and expression of ALS- SOD mutants in transgenic mice produces motor neuron disease. A common phenotype among the ALS-SOD mutations so far investigated is to decrease the affinity for zinc...
  12. Neuronal RNA processing defects in ALS4 caused by SETX mutations
    Craig L Bennett; Fiscal Year: 2013
    ..the different RNA processing pathways found to be affected in ALS4 might also be affected in other forms of motor neuron disease. PUBLIC HEALTH RELEVANCE: Narrative Mutations in senataxin (a DNA/RNA helicase) are known to cause of two ..
  13. Mechanisms of degeneration in the spinal cord and musculoskeletal system in SMA
    SANIYA FAYZULLINA; Fiscal Year: 2013
    ..breaks by homologous recombination in proliferating myoblasts, rather than a secondary consequence of motor neuron disease. This aim will be accomplished by examining, histologically and biochemically, spinal cord MN and skeletal ..
  14. Glutathione in mitochondrial dysfunction and disease progression in ALS-models
    Marcelo R Vargas; Fiscal Year: 2013
    Project Summary ALS, commonly known as Lou Gehrig's disease, is the most common adult motor neuron disease. The disease's primary hallmark is the selective dysfunction and death of the neurons in the motor pathways...
  15. Inositol Lipid regulation of membrane fusion and fission
    Lois S Weisman; Fiscal Year: 2013
    ..Results of these studies should provide new insights into the roles and regulation of PI3,5P2 and will provide a basis for determining to roles of PI3,5P2 in the nervous system. ..
  16. MR and BL Tracking of Stem/Progenitor Cells in the CNS
    Jeff W Bulte; Fiscal Year: 2013
    ..injection, movements, survival, and differentiation) of transplanted cells in two complementary models of motor neuron disease (MND), i.e...
  17. Functional consequences of HSPB1 mutations that result in motor neuron disease
    Stephen J Kolb; Fiscal Year: 2013
    ..Ultimately, this project will lead to the identification of novel targets for the treatment of this devastating class of nervous system disease. ..
  18. Mechanisms of respiratory long-term facilitation
    Gordon S Mitchell; Fiscal Year: 2013
    ..including obstructive sleep apnea and respiratory insufficiency in patients with spinal injury or motor neuron disease (ALS)...
  19. TDP-43 acetylation as a pathogenic modification in ALS &related proteinopathies
    TODD JONATHAN COHEN; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Amyotrophic Lateral Sclerosis (ALS) is a devastating motor neuron disease with a 3-5 year survival rate and no disease-modifying therapies...
  20. Role of Calpastatin in mutant SOD1-mediated motor neuron disease
    Mala V Rao; Fiscal Year: 2010
    Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease and most of the patients die within 3-5 years after disease symptoms are seen. About 90% of the cases the cause of the disease is unknown (sporadic-ALS or S-ALS)...
  21. Functional Coupling of Steps in Genes Expression
    ROBIN E REED; Fiscal Year: 2013
    ..In Specific Aim 2, a major effort is planned to determine how mutations in FUS cause the fatal motor neuron disease amyotrophic lateral sclerosis (ALS)...
  22. Interactions between Urological and Locomotor Systems during Treadmill Training i
    Patricia J Ward; Fiscal Year: 2012
    ..Although partially masked in normal subjects, these reflexes are highly apparent after an upper motor neuron disease or SCI...
  23. Seahorse XF-96 Analyzer for Non-Invasive Monitoring of Mitochondrial Function
    Ahmet Hoke; Fiscal Year: 2010
    ..XF-96 are all neurologists and neuroscientists studying neurodegenerative disease mechanisms, including motor neuron disease, multiple sclerosis, human immunodeficiency virus (HIV) dementia, and peripheral neuropathies...
  24. Mechanistic analysis of axonal transport defects in motor neuron degenerative dis
    Erika L Holzbaur; Fiscal Year: 2012
    ..Dominant mutations in either dynein or dynactin are sufficient to cause motor neuron disease, demonstrating the importance of axonal transport in maintaining healthy motor neurons...
  25. New Insights into Motor Neuron Disease
    John K Fink; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): This investigation will analyze a novel cause of motor neuron disease (MND). We discovered that mutations in the neuropathy target esterase (NTE) gene cause autosomal recessive MND (NTE-MND)...
  26. Delivery of therapeutic genes in motor neuron disease
    Don W Cleveland; Fiscal Year: 2010
    ..in mice and to translate them into the non-human primate in order to develop promising therapies for motor neuron disease. Here we propose (1) to optimize the correction of SMA and treatment of ALS in mouse models, (2) to develop ..
  27. MODELS OF SBMA MOTOR NEURON DEGENERATION
    Albert R La Spada; Fiscal Year: 2013
    ..The discovery of a role for AR normal function in SBMA motor neuron disease suggests that AR may function as a trophic factor in motor neurons...
  28. MICROTUBULE MOTORS STUDIED ON A MOLECULAR SCALE
    Steven M Block; Fiscal Year: 2010
    ..spastic paraplesia, Charcot-Marie-Tooth disease, Kartagener's syndrome, polycystic kidney disease, and motor neuron disease. With the advent of specialized techniques, particularly those in the new field of single molecule ..
  29. Dynactin function in axons, synapses, and neurodegenerative disease
    Thomas Lloyd; Fiscal Year: 2013
    ..mutated in two distinct, non-overlapping autosomal dominant neurodegenerative diseases: one that causes a motor neuron disease called Hereditary Motor Neuropathy type 7B (HMN7B), and the other that is called Perry Syndrome, ..
  30. Fate specification of corticospinal neurons by cell autonomous signaling
    Paola Arlotta; Fiscal Year: 2013
    ..Corticospinal motor neuron (CSMN) degeneration and injury is a key component of motor neuron disease (including ALS), and of spinal cord injury...
  31. Nogo's role in intracellular trafficking
    Noam Y Harel; Fiscal Year: 2010
    ..Finally, Nogo may enhance neuronal survival in the context of motor neuron disease. Better understanding of these roles is crucial as therapies are being developed to block the Nogo pathway ..
  32. Mechanisms of Mutant SOD 1-Mediated Mitochondria Toxicity in the Spinal Cord of A
    Davide Trotti; Fiscal Year: 2012
    ..k.a. Lou Gehrig's disease) is the most common adult motor neuron disease. The disease is characterized by the death of motor neurons in the spinal cord and motor cortex...
  33. Pathologically modified TDP-43 in neurodegenerative diseases
    TANIA FRANCE GENDRON; Fiscal Year: 2012
    ..Mutations in the gene encoding TDP-43 have been identified in ALS and FTLD with or without motor neuron disease, providing a direct link between TDP-43 and neurodegeneration...
  34. Deciphering RNA based mechanisms of neurodegeneration
    Daniela C Zarnescu; Fiscal Year: 2013
    ..In recent years, several RNA binding proteins have been linked to motor neuron disease, including senataxin, angiogenin, TDP-43 and FUS...
  35. Motor Neuron Disease in Mouse Models of ALS: Where Does The End Begin
    Carol Milligan; Fiscal Year: 2013
    ..In this way we hope to open up new avenues for the treatment of motor neuron disease and other neurodegenerative diseases that involve early loss of axons and synapses...
  36. X-RAY STUDIES OF SOD IN AMYOTROPHIC LATERAL SCLEROSIS
    PETER JOHN HART; Fiscal Year: 2010
    ..have been linked to an inherited form of amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease, motor neuron disease)...
  37. A Drosophila model of motor neuron disease using mutations in P150 / Dynactin.
    Thomas Lloyd; Fiscal Year: 2012
    ..The candidate, Thomas Lloyd M.D., Ph.D. proposes to characterize and utilize a novel model of motor neuron disease using the powerful genetic organism Drosophila melanogaster...
  38. Elucidating the Mechanisms Underlying Mutant TDP43-induced Neurodegeneration
    Sami Barmada; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, and despite its initial description over 100 years ago by Jean-Martin Charcot, there remains no effective therapy for the ..
  39. Trophic Factor Signaling and Motor Neuron Death
    Robert G Kalb; Fiscal Year: 2013
    ..In specific aim #2, we will determine if loss of FOXO3a ameliorates or exacerbates the mutant SOD mouse motor neuron disease. In the course of our investigations of FOXO3a, we found a marine sponge compound (Psammaplysene A, PA) ..
  40. Molecular Mechanisms of CTIP2 Function in Corticospinal Motor Neuron Development
    Jeffrey D Macklis; Fiscal Year: 2013
    ..neurons, and clinically important as the brain neurons that degenerate in amyotrophic lateral sclerosis / motor neuron disease (ALS/MND) and whose axonal injury is central to loss of motor function in spinal cord injury...
  41. Senataxin mutations in familial motor neuron disease (ALS4) and Ataxia (AOA2)
    Gwenn A Garden; Fiscal Year: 2010
    ..Since there is currently no cure or preventive treatment for these conditions, any knowledge gained has the potential to provide future diagnostic and therapeutic interventions for these patients. ..
  42. Contribution of AMPK to motor neuron disease
    MARIA ANGELINA LIM; Fiscal Year: 2012
    ..Based on these preliminary results, we hypothesize that specific bioenergetic defects in mSODI-induced motor neuron disease activate AMPK, and that AMPK activation adversely affects neuronal survival...
  43. Intermittent Hypoxia-Induced Inflammation Modulates Respiratory Plasticity
    Jyoti J Watters; Fiscal Year: 2013
    ..Our long-range goal is to harness and promote respiratory plasticity as a therapeutic strategy to treat devastating breathing disorders, such as during cervical spinal injury or motor neuron disease.
  44. The role of UCHL1 on the health and stability of upper motor neurons
    Pembe Hande Ozdinler; Fiscal Year: 2013
    ..This proposal will bring a mechanistic insight into upper motor neuron degeneration and will reveal the role of UCHL1, and more broadly the function of improper UPS on the health and stability of upper motor neurons. ..
  45. MOLECULAR ANALYSIS OF NUCLEAR PORE COMPLEX FUNCTION
    Susan R Wente; Fiscal Year: 2013
    ..will be measured for a human GLE1 mutant (gle1-FINmajor) that is causally linked to a lethal fetal motor neuron disease. Direct protein-protein interactions that are altered by the gle1-FINmajor mutant will also be identified...
  46. New Frontiers in Neurodegenerative Disease Research
    David L Woodland; Fiscal Year: 2012
    ..since genes causing familial Alzheimer's disease, Parkinson's disease, Huntington's disease, motor neuron disease and other neurodegenerative disorders were identified...
  47. Muscle and neuromuscular junctions in spinal muscular atrophy
    CHARLOTTE JANE SUMNER; Fiscal Year: 2013
    ..provided by applicant): Spinal muscular atrophy (SMA) is a currently untreatable, autosomal recessive motor neuron disease that is the leading inherited cause of infant mortality...
  48. A Large Animal Model of SMA
    Monique A Lorson; Fiscal Year: 2013
    ..SMA, the most common inherited motor neuron disease, occurs in ~1:8,000 live births and has a carrier frequency of ~1:40;however, no cure exists...
  49. Toxicodietary and genetic determinants of susceptibility to neurodegeneration
    DANIEL DESIRE TSHALA-KATUMBAY; Fiscal Year: 2013
    ..The overall goal of this proposal meshes well with the global health mission of the NIH while integrating the institute-specific missions of FIC, NIEHS, NINDS, and NICHD. ..
  50. Tract-Specific Analysis of Brain White Matter
    James C Gee; Fiscal Year: 2010
    ..Specifically, the proposed study of upper motor neuron disease in ALS, with specific biological hypotheses, will help define the effects of the proposed tract-specific ..
  51. TDP-43 Proteinopathies in ALS-Dementia
    Virginia M Lee; Fiscal Year: 2013
    Ubiquitin positive inclusions are found in amyotrophic lateral sclerosis (ALS), a prototypic motor neuron disease and frontotemporal lobar degeneration (FTLD), the second most common dementia after Alzheimer's disease in patients <..
  52. SUPEROXIDE DISMUTASE STRUCTURES AND LOU GEHRIGS DISEASE
    John A Tainer; Fiscal Year: 2013
    ..Lateral Sclerosis (FALS), an inherited variety of ALS (or Lou Gehrig's disease), the most common human motor neuron disease. We, and others have discovered that FALS SOD mutants have defects in fold and assembly, and form fibrous ..
  53. Parkinson's Disease and Mechanisms of Fast Axonal Transport
    Ramona Pufan; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): The most common adult-onset neurodegenerative motor neuron disease is Parkinson's disease (PD)...
  54. Structure/Function of Mn and Fe Superoxide Dismutases and Related Enzymes
    THOMAS CHRISTIAN BRUNOLD; Fiscal Year: 2011
    ..anion and free cysteine have been shown to play a role in several neurodegenerative diseases, including motor neuron disease, Parkinson disease, and Alzheimer disease...
  55. Tissue-specific pathways of copper homeostasis in growth and development
    Michael J Petris; Fiscal Year: 2013
    ..Other diseases attributable to mutations in ATP7A include occipital horn syndrome and peripheral motor neuron disease. Moreover, copper and/or the ATP7A protein is implicated in pathogenic processes underlying certain ..
  56. NOVEL INSIGHTS INTO MOTOR NEURON DISEASE
    John K Fink; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Abstract This investigation will analyze a novel cause of motor neuron disease (MND). We discovered that mutations in neuropathy target esterase (NTE) cause MND (NTE-MND)...
  57. Pathophysiology of environmentally-induced protein malfolding
    Glenn I Fishman; Fiscal Year: 2010
    ..important role neurodegenerative conditions, such as Parkinson's Disease, Alzheimer's Disease and Motor Neuron Disease. Accumulating evidence suggests that environmental agents may contribute to the pathophysiology of these ..
  58. Selective Vulnerability in Frontotemporal Dementia
    William W Seeley; Fiscal Year: 2013
    ..Some patients with FTD develop motor neuron disease (MND), which shortens the disease course and provides a window into early FTD anatomical deficits...
  59. Genetic Control of Motor Neuron Development and Function
    Samuel L Pfaff; Fiscal Year: 2013
    ..for the survival and proper function of post natal motor neurons, since this could shed new light on motor neuron disease pathways...
  60. Envronment-Sensitive genes in motoneuron degeneration
    Teepu Siddique; Fiscal Year: 2010
    ..This investigation will establish genetic and environmental risks, and lead to rational treatment and prevention of disabling fatal disorders of PLS and SALS. ..
  61. Multi-Center Validation of Biomarkers for Motor Neuron Disease
    Merit E Cudkowicz; Fiscal Year: 2010
    ..Our validated protein and antibody based biomarkers for ALS will create quick diagnostic tests for ALS. ..
  62. Using Drosophila Neurons to Identify Mechanisms that Control Microtubule Polarity
    Melissa Rolls; Fiscal Year: 2013
    ..Our results will form a foundation for understanding neurological diseases ranging from motor neuron disease to Williams syndrome, as they result from perturbations in microtubule organization or trafficking.
  63. Neurodegeneration in Aging Retarded Mice
    Roger Albin; Fiscal Year: 2009
    ..We would be able to extend these approaches also to other neurodegenerations such as Alzheimer disease and Motor Neuron disease. PUBLIC HEALTH RELEVANCE The onset of most degenerative brain diseases, like Alzheimer disease and ..
  64. microRNA biogenesis and function in spinal muscular atrophy
    Zissimos Mourelatos; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is a common motor neuron disease and one of the leading genetic causes of death of young children...
  65. Intravenous non-viral gene therapy for amyotrophic lateral sclerosis
    Gyula Acsadi; Fiscal Year: 2006
    ..DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is the most prevalent lethal motor neuron disease in adults and there is no effective therapy available...
  66. INTERMEDIATE FILAMENTS--MOLECULAR APPROACH TO FUNCTION
    STEPHEN TAPSCOTT; Fiscal Year: 1990
    ..proteins and vimentin in the neurofibrillary tangles of Alzheimer's disease, and neurofilaments in motor neuron disease; however, the current ignorance of normal IF regulation and function makes these findings difficult to ..
  67. Target Validation for Neurogenerative Disease Using Conditional RNAi in vivo
    MICHELE MAXWELL; Fiscal Year: 2009
    ..are designed directly to determine at what point, during the life of an animal engineered to develop motor neuron disease, a reduction in the amount of mutant SOD1 protein will provide a significant therapeutic benefit...
  68. MOTOR NEURON DEGENERATION IN A MODEL OF ALS
    Erik Pioro; Fiscal Year: 1999
    ..The wobbler mouse is the most studied animal model of human motor neuron disease and its pathology closely resembles that seen in ALS...
  69. GENETIC CONTROL OF NEUROMUSCULAR DEGENERATION IN MICE
    Gregory Cox; Fiscal Year: 2002
    ..of its phenotypic expression (Mnm) will allow us to experimentally determine the mechanisms responsible for motor neuron disease. Toward this goal, we are employing sophisticated genetic approaches to identify the critical cell-neuron ..
  70. MOLECULAR PATHOGENESIS OF FELINE SPINAL MUSCULAR ATROPHY
    JOHN FYFE; Fiscal Year: 2002
    ..Characterization of this animal model will address the need to better understand the mechanisms of motor neuron disease in humans and, potentially, provide a system in which to test new therapeutic protocols...
  71. Genes and Genetic Models in Motor Neuron Disorders
    Teepu Siddique; Fiscal Year: 2007
    ..Interaction will be confirmed by dual labeled confocal microscopy and FRET analysis. ..
  72. NO DAMAGE TO FOLATE CYCLE IN THE CENTRAL NERVOUS SYSTEM
    Kenneth Hensley; Fiscal Year: 2005
    ..are compromised in aged humans, and more so in cases of dementia (such as Alzheimer's disease, AD) or motor neuron disease (such as amyotrophic lateral sclerosis, ALS)...