nerve degeneration

Summary

Summary: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.

Top Publications

  1. ncbi The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics
    John Hardy
    Laboratories of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Science 297:353-6. 2002
  2. ncbi Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology
    Alexander Zimprich
    Department of Neurodegenerative Disease, Hertie Institute for Clinical Brain Research, University of Tubingen, 72076 Tubingen, Germany
    Neuron 44:601-7. 2004
  3. ncbi Neuroinflammation in Parkinson's disease: a target for neuroprotection?
    Etienne C Hirsch
    INSERM, UMRS 975, Centre de Recherche de l Institut du Cerveau et de la Moelle Epiniere, Experimental Therapeutics of Neurodegeneration, Paris, France
    Lancet Neurol 8:382-97. 2009
  4. pmc Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway
    Seija Lehnardt
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:8514-9. 2003
  5. pmc Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis
    Koji Yamanaka
    Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093 0670, USA
    Nat Neurosci 11:251-3. 2008
  6. ncbi Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation
    Holly Oakley
    Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 26:10129-40. 2006
  7. pmc Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss
    Sharon G Kujawa
    Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 29:14077-85. 2009
  8. ncbi Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
    J S Steffan
    Department of Psychiatry and Human Behavior, Gillespie 2121, University of California, Irvine, California 92697, USA
    Nature 413:739-43. 2001
  9. ncbi Inflammatory neurodegeneration and mechanisms of microglial killing of neurons
    Guy C Brown
    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK
    Mol Neurobiol 41:242-7. 2010
  10. 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

Detail Information

Publications304 found, 100 shown here

  1. ncbi The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics
    John Hardy
    Laboratories of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Science 297:353-6. 2002
    ..The rest of the disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between Abeta production and Abeta clearance...
  2. ncbi Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology
    Alexander Zimprich
    Department of Neurodegenerative Disease, Hertie Institute for Clinical Brain Research, University of Tubingen, 72076 Tubingen, Germany
    Neuron 44:601-7. 2004
    ..Hence, LRRK2 may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism...
  3. ncbi Neuroinflammation in Parkinson's disease: a target for neuroprotection?
    Etienne C Hirsch
    INSERM, UMRS 975, Centre de Recherche de l Institut du Cerveau et de la Moelle Epiniere, Experimental Therapeutics of Neurodegeneration, Paris, France
    Lancet Neurol 8:382-97. 2009
    ....
  4. pmc Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway
    Seija Lehnardt
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:8514-9. 2003
    ..In contrast, animals bearing a loss-of-function mutation in the tlr4 gene are resistant to neuronal injury in the same model. The present study demonstrates a mechanistic link among innate immunity, TLRs, and neurodegeneration...
  5. pmc Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis
    Koji Yamanaka
    Ludwig Institute for Cancer Research and Department of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093 0670, USA
    Nat Neurosci 11:251-3. 2008
    ..These findings demonstrate that mutant astrocytes are viable targets for therapies for slowing the progression of non-cell autonomous killing of motor neurons in ALS...
  6. ncbi Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation
    Holly Oakley
    Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 26:10129-40. 2006
    ..Thus, 5XFAD mice rapidly recapitulate major features of AD amyloid pathology and may be useful models of intraneuronal Abeta42-induced neurodegeneration and amyloid plaque formation...
  7. pmc Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss
    Sharon G Kujawa
    Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 29:14077-85. 2009
    ..This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage...
  8. ncbi Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
    J S Steffan
    Department of Psychiatry and Human Behavior, Gillespie 2121, University of California, Irvine, California 92697, USA
    Nature 413:739-43. 2001
    ..These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neurodegeneration seen in Huntington's disease and other polyglutamine-repeat diseases, even after the onset of symptoms...
  9. ncbi Inflammatory neurodegeneration and mechanisms of microglial killing of neurons
    Guy C Brown
    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK
    Mol Neurobiol 41:242-7. 2010
    ..Finally, microglial phagocytosis of these stressed neurons may contribute to their loss...
  10. 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...
  11. ncbi Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration
    L C Schmued
    Division of Neurotoxicology, National Center for Toxicological Research FDA, 3900 NCTR Road, 72079 9502, Jefferson, AR 72079 9502, USA
    Brain Res 874:123-30. 2000
    ..Like Fluoro-Jade, Fluoro-Jade B is compatible with a number of other labeling procedures including immunofluorescent and fluorescent Nissl techniques...
  12. ncbi A block of autophagy in lysosomal storage disorders
    Carmine Settembre
    Telethon Institute of Genetics and Medicine TIGEM, Naples, Italy
    Hum Mol Genet 17:119-29. 2008
    ..These data identify LSDs as 'autophagy disorders' and suggest the presence of common mechanisms in the pathogenesis of these and other neurodegenerative diseases...
  13. pmc Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma
    Janey L Wiggs
    Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America
    PLoS Genet 8:e1002654. 2012
    Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease...
  14. ncbi A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis
    Ivana Nikic
    Research Unit Therapy Development, Institute of Clinical Neuroimmunology, Ludwig Maximilians Universitat Munchen, Munich, Germany
    Nat Med 17:495-9. 2011
    ..Finally, axonal changes consistent with FAD can be detected in acute human multiple sclerosis lesions. In summary, our data suggest that inflammatory axon damage might be spontaneously reversible and thus a potential target for therapy...
  15. ncbi Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles
    C W Wittmann
    Department of Pathology, Division of Neuropathology, Brigham and Women s Hospital and Harvard Medical School, 221 Longwood Avenue, Room 514, Boston, MA 02115, USA
    Science 293:711-4. 2001
    ..This fly model may allow a genetic analysis of the cellular mechanisms underlying tau neurotoxicity...
  16. ncbi Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors
    Hirofumi Nakatomi
    Department of Neurobiology, The University of Tokyo Graduate School of Medicine, 7 3 1 Hongo, Bunkyo ku, Japan
    Cell 110:429-41. 2002
    ..These results expand the possibility of novel neuronal cell regeneration therapies for stroke and other neurological diseases...
  17. 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...
  18. ncbi Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal Aβ aggregation in the 5XFAD mouse model of Alzheimer's disease
    Sadim Jawhar
    Division of Molecular Psychiatry, Alzheimer Ph D, Graduate School, Department of Psychiatry, University of Goettingen, Von Siebold Str 5, 37075 Goettingen, Germany
    Neurobiol Aging 33:196.e29-40. 2012
    ..In addition, comparable to the APP/PS1KI mouse model, 5XFAD mice develop an age-dependent axonopathy likely contributing to the behavioral deficits...
  19. pmc Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein and LRRK2 in the brain
    Lauren G Friedman
    Department of Neurology, Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Neurosci 32:7585-93. 2012
    ..Our findings implicate dysfunctional autophagy as one of the failing cellular mechanisms involved in the pathogenesis of idiopathic PD...
  20. pmc Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models
    Antony A Cooper
    School of Biological Sciences, University of Missouri Kansas City, Kansas City, MO 64110, USA
    Science 313:324-8. 2006
    ..Thus, synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable...
  21. ncbi Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70
    J M Warrick
    Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Genet 23:425-8. 1999
    ..Our studies indicate that HSP70 or related molecular chaperones may provide a means of treating these and other neurodegenerative diseases associated with abnormal protein conformation and toxicity...
  22. ncbi Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin
    Jeehye Park
    Nature 441:1157-61. 2006
    ..Taken together, our genetic evidence clearly establishes that Parkin and PINK1 act in a common pathway in maintaining mitochondrial integrity and function in both muscles and dopaminergic neurons...
  23. pmc Axon degeneration: molecular mechanisms of a self-destruction pathway
    Jack T Wang
    Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA
    J Cell Biol 196:7-18. 2012
    ..with those in acute injuries, and expression of the Wallerian degeneration slow (WldS) transgene delays nerve degeneration in both events, indicating a common mechanism of axonal self-destruction in traumatic injuries and ..
  24. pmc Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson's disease
    María Clara Pott Godoy
    Fundacion Instituto Leloir, FBMC UBA, CONICET, Patricias Argentinas 435, 1405 Buenos Aires, Argentina
    Brain 131:1880-94. 2008
    ....
  25. pmc Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans
    Richard Nass
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 6420, USA
    Proc Natl Acad Sci U S A 99:3264-9. 2002
    ..6-OHDA-triggered neural degeneration does not require the CED-3/CED-4 cell death pathway, but is abolished by the genetic disruption of the C. elegans DAT...
  26. ncbi Chronic systemic pesticide exposure reproduces features of Parkinson's disease
    R Betarbet
    Department of Neurology, Emory University, 1639 Pierce Drive, WMB 6000, Atlanta, Georgia 30322, USA
    Nat Neurosci 3:1301-6. 2000
    ..These results indicate that chronic exposure to a common pesticide can reproduce the anatomical, neurochemical, behavioral and neuropathological features of PD...
  27. ncbi Intraneuronal Abeta, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimer's disease
    D C Crowther
    Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 2XY, UK
    Neuroscience 132:123-35. 2005
    ..Moreover it provides a platform to dissect the pathways of neurodegeneration in Alzheimer's disease and to develop novel therapeutic interventions...
  28. ncbi Disorganized microtubules underlie the formation of retraction bulbs and the failure of axonal regeneration
    Ali Erturk
    Max Planck Institute of Neurobiology, Axonal Growth and Regeneration, 82152 Martinsried, Germany
    J Neurosci 27:9169-80. 2007
    ..Our data pinpoint microtubules as a key regulatory target for axonal regeneration...
  29. pmc Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss
    Luke S Tain
    Medical Research Council Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, UK
    Nat Neurosci 12:1129-35. 2009
    ..Thus, in conjunction with recent findings, our results suggest that pharmacologic stimulation of 4E-BP activity may represent a viable therapeutic approach for multiple forms of parkinsonism...
  30. ncbi Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients
    Ranjan Dutta
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA
    Ann Neurol 59:478-89. 2006
    ..Development of neuroprotective therapies will require elucidation of the molecular mechanisms by which neurons and axons degenerate...
  31. ncbi In vivo imaging of axonal degeneration and regeneration in the injured spinal cord
    Martin Kerschensteiner
    Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Nat Med 11:572-7. 2005
    ..These results suggest that time-lapse imaging of spinal cord injury may provide a powerful analytical tool for assessing the pathogenesis of spinal cord injury and for evaluating therapies that enhance regeneration...
  32. ncbi Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide
    Christian Haass
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    Nat Rev Mol Cell Biol 8:101-12. 2007
    ..Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins...
  33. ncbi Progressive ganglion cell degeneration precedes neuronal loss in a mouse model of glaucoma
    Brian P Buckingham
    Department of Neurological Surgery, University of Washington, Seattle, Washington 98104, USA
    J Neurosci 28:2735-44. 2008
    ..This progression of degeneration suggests a need to examine the RGC axon as a locus of pathology in glaucoma...
  34. pmc Parkin deficiency increases vulnerability to inflammation-related nigral degeneration
    Tamy C Frank-Cannon
    Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9040, USA
    J Neurosci 28:10825-34. 2008
    ....
  35. ncbi Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies
    Michael L Kramer
    Prion and Dementia Research Unit, Institute of Neuropathology, University of Goettingen, 37075 Goettingen, Germany
    J Neurosci 27:1405-10. 2007
    ..This concept may also be valid for Parkinson's disease...
  36. pmc Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation
    Hai Yan Wu
    Department of Neurology Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurosci 30:2636-49. 2010
    ..Thus, Abeta appears to mediate the neurodegeneration of AD, at least in part, by activation of CaN and subsequent NFAT-mediated downstream cascades...
  37. ncbi Early synaptic pathophysiology in neurodegeneration: insights from Huntington's disease
    Austen J Milnerwood
    Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, Canada
    Trends Neurosci 33:513-23. 2010
    ..Further understanding the primary effects of gene mutations associated with late-onset neurodegeneration should translate to novel treatments for HD families and guide therapeutic strategies for other neurodegenerative diseases...
  38. 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
    ..Since Bcl-2 acts strictly on neuronal cell body survival without compensating for nerve degeneration in pmn/pmn/bcl-2 mice, this proto-oncogene would not in itself be sufficient for treatment of ..
  39. ncbi A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration
    J G Hodgson
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
    Neuron 23:181-92. 1999
    ..These mice demonstrate that initial neuronal cytoplasmic toxicity is followed by cleavage of htt, nuclear translocation of htt N-terminal fragments, and selective neurodegeneration...
  40. ncbi Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss
    Axel Petzold
    Department of Neuroimmunology, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
    J Neurol Sci 233:183-98. 2005
    ..With reference to the present symposium on multiple sclerosis, the current literature on body fluid levels of neurofilaments in demyelinating disease is summarised...
  41. 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...
  42. pmc Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration
    Masaaki Komatsu
    Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA
    Proc Natl Acad Sci U S A 104:14489-94. 2007
    ..Our study implicates impairment of axonal autophagy as a possible mechanism for axonopathy associated with neurodegeneration...
  43. pmc The parkinsonian mimetic, MPP+, specifically impairs mitochondrial transport in dopamine axons
    Jeong Sook Kim-Han
    Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
    J Neurosci 31:7212-21. 2011
    ..Since these drugs also rescued processes from degeneration, these findings emphasize the need to develop therapeutics aimed at axons as well as cell bodies to preserve "normal" circuitry and function as long as possible...
  44. pmc Intraneuronal pyroglutamate-Abeta 3-42 triggers neurodegeneration and lethal neurological deficits in a transgenic mouse model
    Oliver Wirths
    Division of Molecular Psychiatry, Department of Psychiatry, University of Goettingen, Von Siebold Strasse 5, Goettingen, Germany
    Acta Neuropathol 118:487-96. 2009
    ..Although the TBA2 model lacks important AD-typical neuropathological features like tangles and hippocampal degeneration, it clearly demonstrates that intraneuronal Abeta(3(pE)-42) is neurotoxic in vivo...
  45. pmc Mechanisms of acute axonal degeneration in the optic nerve in vivo
    Johanna Knöferle
    Departments of Neurology and Neuropathology, University Medicine, Georg August University, 37075 Gottingen, Germany
    Proc Natl Acad Sci U S A 107:6064-9. 2010
    ..Both processes are proposed to be major targets for the manipulation of axonal degeneration in future therapeutic settings...
  46. ncbi Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALS
    Susan E Browne
    Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 E 68th Street, A 502, New York, NY 10021, USA
    Neurobiol Dis 22:599-610. 2006
    ....
  47. pmc Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal
    Sung Chun Tang
    Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA
    Exp Neurol 213:114-21. 2008
    ..Our findings suggest that TLR4 signaling increases the vulnerability of neurons to Abeta and oxidative stress in AD, and identify TLR4 as a potential therapeutic target for AD...
  48. ncbi Microglia
    Denise van Rossum
    Institute for Neuropathology, University of Gottingen, D 37075 Gottingen, Germany
    Metab Brain Dis 19:393-411. 2004
    ....
  49. ncbi Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration
    Sreeganga Chandra
    Center for Basic Neuroscience, Department of Molecular Genetics, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Cell 123:383-96. 2005
    ....
  50. ncbi The synaptic vesicle protein CSP alpha prevents presynaptic degeneration
    Rafael Fernandez-Chacon
    Center for Basic Neuroscience, Department of Molecular Genetics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75390, USA
    Neuron 42:237-51. 2004
    ....
  51. pmc Axonal degeneration is mediated by the mitochondrial permeability transition pore
    Sebastian A Barrientos
    Department of Physiology, Faculty of Biology, Catholic University of Chile, Santiago 8331150, Chile
    J Neurosci 31:966-78. 2011
    ....
  52. ncbi Patterns of retinal nerve fiber layer loss in multiple sclerosis patients with or without optic neuritis and glaucoma patients
    Markus Bock
    Cecilie Vogt Clinic, Charite Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany
    Clin Neurol Neurosurg 112:647-52. 2010
    ....
  53. ncbi Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease
    David Sulzer
    Department of Neurology, Black 309, 650 West, 168th Street, Columbia University, New York State Psychiatric Institute, New York City, NY 10032, USA
    Trends Neurosci 30:244-50. 2007
    ..We discuss the properties of substantia nigra dopamine neurons that might make them particular targets of such multiple hits...
  54. pmc Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson's and Lewy body diseases
    Brian Spencer
    Department of Neurosciences, University of California, San Diego, La Jolla, California 92093 0624, USA
    J Neurosci 29:13578-88. 2009
    ..Thus, beclin 1 plays an important role in the intracellular degradation of alpha-syn either directly or indirectly through the autophagy pathway and may present a novel therapeutic target for LBD/PD...
  55. ncbi RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila
    Peng Jin
    Department of Human Genetics, Emory University, Atlanta, GA 30322, USA
    Neuron 39:739-47. 2003
    ..These results demonstrate that neurodegenerative phenotype associated with fragile X premutation is indeed caused by the lengthened rCGG repeats and provide the first in vivo experimental demonstration of RNA-mediated neurodegeneration...
  56. pmc A pathologic cascade leading to synaptic dysfunction in alpha-synuclein-induced neurodegeneration
    David A Scott
    Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA
    J Neurosci 30:8083-95. 2010
    ..Collectively the data suggest a previously unknown cascade of events where pathologic alpha-synuclein leads to a loss of a number of critical presynaptic proteins, thereby inducing functional synaptic deficits...
  57. ncbi A model to study differences between primary and secondary degeneration of retinal ganglion cells in rats by partial optic nerve transection
    Hana Levkovitch-Verbin
    Department of Ophthalmology, Wilmer Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA
    Invest Ophthalmol Vis Sci 44:3388-93. 2003
    ..To use a rat model of optic nerve injury to differentiate primary and secondary retinal ganglion cell (RGC) injury...
  58. ncbi Molecular pathways of neurodegeneration in Parkinson's disease
    Ted M Dawson
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Science 302:819-22. 2003
    ..Strategies aimed at restoring complex I activity, reducing oxidative stress and alpha-synuclein aggregation, and enhancing protein degradation may hold particular promise as powerful neuroprotective agents in the treatment of PD...
  59. ncbi Intraneuronal amyloid β oligomers cause cell death via endoplasmic reticulum stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo
    Tomohiro Umeda
    Department of Neuroscience, Osaka City University Graduate School of Medicine, Osaka, Japan
    J Neurosci Res 89:1031-42. 2011
    ..Collectively, our findings suggest that intraneuronal Aβ oligomers cause cell death by inducing ER stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo. © 2011 Wiley-Liss, Inc...
  60. ncbi The familial Parkinsonism gene LRRK2 regulates neurite process morphology
    David Macleod
    Departments of Pathology and Neurology, Center for Neurobiology and Behavior and Taub Institute, Columbia University, College of Physicians and Surgeons 15 403, 630 West 168th Street, New York, New York 10032, USA
    Neuron 52:587-93. 2006
    ..Neurons that express PD-associated LRRK2 mutations additionally harbor prominent phospho-tau-positive inclusions with lysosomal characteristics and ultimately undergo apoptosis...
  61. pmc Retrograde axonal transport: pathways to cell death?
    Eran Perlson
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19067, USA
    Trends Neurosci 33:335-44. 2010
    ..Defects in transport are sufficient to induce neurodegeneration, but recent progress suggests that changes in retrograde signaling pathways correlate with rapidly progressive neuronal cell death...
  62. pmc A dual function of V0-ATPase a1 provides an endolysosomal degradation mechanism in Drosophila melanogaster photoreceptors
    W Ryan Williamson
    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Cell Biol 189:885-99. 2010
    ..We propose that V100 exerts a temporally integrated dual function that increases neuronal degradative capacity...
  63. ncbi Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders
    Byron Caughey
    NIAID, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, USA
    Annu Rev Neurosci 26:267-98. 2003
    ..This review focuses on recent experimental studies aimed at identification and characterization of the neurotoxic protein aggregates...
  64. pmc TTC, fluoro-Jade B and NeuN staining confirm evolving phases of infarction induced by middle cerebral artery occlusion
    Fudong Liu
    Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06032, USA
    J Neurosci Methods 179:1-8. 2009
    ..As the infarct is complete by 24h and even earlier in the striatum, even the most efficacious neuroprotective therapies are unlikely to show any efficacy if given after this point...
  65. ncbi Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease
    C Cunningham
    CNS Inflammation Group, Southampton Neuroscience Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
    Eur J Neurosci 17:2147-55. 2003
    ..We have demonstrated a neuropathological correlate of an early behavioural deficit in prion disease and suggest that this should allow insights into the first steps of the neuropathogenesis of prion diseases...
  66. ncbi Quantifying axonal loss after optic neuritis with optical coherence tomography
    Fiona Costello
    Division of Neurology, Ottawa, Ontario Canada
    Ann Neurol 59:963-9. 2006
    ..To determine to what degree changes in retinal nerve fiber layer (RNFL) thickness after optic neuritis (ON) correlate with either visual recovery or impairment...
  67. pmc Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease
    Y Du
    Departmens of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Proc Natl Acad Sci U S A 98:14669-74. 2001
    ..Thus, NO appears to play an important role in MPTP neurotoxicity. Neuroprotective tetracyclines may be effective in preventing or slowing the progression of Parkinson's and other neurodegenerative diseases...
  68. pmc A Drosophila model for LRRK2-linked parkinsonism
    Zhaohui Liu
    Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 105:2693-8. 2008
    ..These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention...
  69. ncbi Inhibition of FK506 binding proteins reduces alpha-synuclein aggregation and Parkinson's disease-like pathology
    Melanie Gerard
    Laboratories of Biochemistry, Interdisciplinary Research Centre, Katholieke Universiteit Leuven Kortrijk, Flanders, Belgium
    J Neurosci 30:2454-63. 2010
    ..Our data explain previously described neuroregenerative and neuroprotective effects of immunophilin ligands and validate FKBPs as a novel drug target for the causative treatment of PD...
  70. ncbi Microglial clearance function in health and disease
    I Napoli
    Institute of Reconstructive Neurobiology, University Bonn Life and Brain Center, University Bonn and Hertie Foundation, Sigmund Freud Str 25, 53127 Bonn, Germany
    Neuroscience 158:1030-8. 2009
    ..Insufficient clearance by microglia appears to be prevalent in neurodegenerative diseases such as Alzheimer's disease...
  71. ncbi Near infrared light reduces oxidative stress and preserves function in CNS tissue vulnerable to secondary degeneration following partial transection of the optic nerve
    Melinda Fitzgerald
    Experimental and Regenerative Neurosciences, The University of Western Australia, Crawley, Western Australia, Australia
    J Neurotrauma 27:2107-19. 2010
    ..To our knowledge, this is the first demonstration that 670-nm NIR light can reduce oxidative stress and improve function in the CNS following traumatic injury in vivo...
  72. 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
    ..Thus, autophagy seems to be activated and upregulated in the cytoplasm of motor neurons and may be involved in the mechanisms of neurodegeneration of motor neurons in sporadic ALS...
  73. pmc Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons
    Jonathan Gilley
    The Babraham Institute, Babraham Research Campus, Cambridge, UK
    PLoS Biol 8:e1000300. 2010
    ..Endogenous Nmnat2 represents an exciting new therapeutic target for axonal disorders...
  74. 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
    ..Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology. Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons...
  75. ncbi TDP-43 and FUS/TLS: cellular functions and implications for neurodegeneration
    Fabienne C Fiesel
    Department of Neurodegeneration, Faculty of Medicine, University of Tuebingen, Tuebingen, Germany
    FEBS J 278:3550-68. 2011
    ..In this minireview the specific functions of TDP-43 and FUS are described and discussed in the context of how TDP-43 and FUS may contribute to the pathogenesis of frontotemporal lobar degeneration and amyotrophic lateral sclerosis...
  76. ncbi Severely dystrophic axons at amyloid plaques remain continuous and connected to viable cell bodies
    Robert Adalbert
    The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, UK
    Brain 132:402-16. 2009
    ....
  77. pmc Drosophila NMNAT maintains neural integrity independent of its NAD synthesis activity
    R Grace Zhai
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS Biol 4:e416. 2006
    ..Our data indicate an NAD-independent requirement of NMNAT for maintaining neuronal integrity that can be exploited to protect neurons from neuronal activity-induced degeneration by overexpression of the protein...
  78. ncbi Tau-mediated neurodegeneration in Alzheimer's disease and related disorders
    Carlo Ballatore
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, Pennsylvania 19104 4283, USA
    Nat Rev Neurosci 8:663-72. 2007
    ....
  79. ncbi The role of microglia and macrophages in the pathophysiology of the CNS
    G Stoll
    Department of Neurology, Heinrich Heine University, Dusseldorf, Germany
    Prog Neurobiol 58:233-47. 1999
    ..In the human acquired immunodeficiency syndrome (AIDS) virus infected macrophages probably introduce the virus to the CNS and in concert with microglia are involved in the pathophysiology of the AIDS dementia complex...
  80. ncbi Inflammation and neurodegeneration in Parkinson's disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research and the Pacific Parkinson s Research Centre, University of British Columbia, 2255 Westbrook Mall, Vancouver, BC, Canada V6T 1Z3
    Parkinsonism Relat Disord 10:S3-7. 2004
    ..The upregulation appears greater than that found in inflamed arthritic joints. These data support the hypothesis that chronic inflammation may play an important role, if secondary, in the pathogenesis of PD...
  81. ncbi Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease
    Shiyong Peng
    Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
    J Neurochem 93:1412-21. 2005
    ....
  82. ncbi Neurotoxic effects induced by the Drosophila amyloid-beta peptide suggest a conserved toxic function
    Katia Carmine-Simmen
    Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Neurobiol Dis 33:274-81. 2009
    ..In addition, we found that the behavioral phenotypes precede extracellular amyloid deposit formation, supporting results that intracellular Abeta plays a key role in AD...
  83. ncbi Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons
    Larry C Schmued
    Division of Neurotoxicology, National Center for Toxicological Research FDA, Jefferson, AR 72079, USA
    Brain Res 1035:24-31. 2005
    ..Triple labeling was accomplished by staining degenerating neurons with Fluoro-Jade C, cell nuclei with DAPI and activated astrocytes with GFAP immunofluoresence...
  84. ncbi Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease
    Wei Zhang
    Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences National Institutes of Health, Research Triangle Park, North Carolina, USA
    FASEB J 19:533-42. 2005
    ..Finally, NADPH oxidase could be an ideal target for potential pharmaceutical intervention, given that it plays a critical role in alpha-synuclein-mediated microglial activation and associated neurotoxicity...
  85. pmc Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention
    MALU G TANSEY
    Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30324, USA
    Neurobiol Dis 37:510-8. 2010
    ....
  86. ncbi High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation
    L Mucke
    Gladstone Institute of Neurological Disease, Department of Neurology, and Neuroscience Program, University of California, San Francisco, California 94141 9100, USA
    J Neurosci 20:4050-8. 2000
    ..Our results support the emerging view that plaque-independent Abeta toxicity plays an important role in the development of synaptic deficits in AD and related conditions...
  87. ncbi Induction of autophagy in axonal dystrophy and degeneration
    Qing Jun Wang
    Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, New York, New York 10021, USA
    J Neurosci 26:8057-68. 2006
    ..We propose that induction of autophagy serves as an early stress response in axonal dystrophy and may participate in the remodeling of axon structures...
  88. ncbi Role of nitric oxide in inflammation-mediated neurodegeneration
    Bin Liu
    Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences National Institutes of Health, Research Triangle Park, North Carolina 27710, USA
    Ann N Y Acad Sci 962:318-31. 2002
    ..Among these agents, the opioid receptor antagonist naloxone, especially its non-opioid enantiomer (+)-naloxone, promises to be of potential therapeutic value for the treatment of inflammation-related diseases...
  89. pmc The relation between inflammation and neurodegeneration in multiple sclerosis brains
    Josa M Frischer
    Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A 1090 Wien, Austria
    Brain 132:1175-89. 2009
    ..It further indicates that the disease processes of multiple sclerosis may die out in aged patients with long-standing disease...
  90. ncbi A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS
    Seija Lehnardt
    Center for Anatomy, Institute for Cell Biology and Neurobiology, Charite Universitaetsmedizin Berlin, 10117 Berlin, Germany
    J Neurosci 28:2320-31. 2008
    ..This is the first evidence of an endogenous molecular pathway common to many forms of neuronal injury that bidirectionally links CNS inflammation with neurodegeneration...
  91. ncbi A Drosophila model of Parkinson's disease
    M B Feany
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 404:394-8. 2000
    ..Our Drosophila model thus recapitulates the essential features of the human disorder, and makes possible a powerful genetic approach to Parkinson's disease...
  92. ncbi Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models
    Shinjiro Kaneko
    Division of Neuroscience, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 26:9794-804. 2006
    ..Finally, we demonstrate that delayed NAm treatment is also beneficial to EAE models, pointing to the therapeutic potential of NAm as a protective agent for EAE and perhaps MS patients...
  93. pmc Nicotinamide mononucleotide adenylyl transferase-mediated axonal protection requires enzymatic activity but not increased levels of neuronal nicotinamide adenine dinucleotide
    Yo Sasaki
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 29:5525-35. 2009
    ..These results provide the possibility of a role for new Nmnat enzymatic activity in axonal protection in addition to NAD(+) synthesis...
  94. ncbi Neuro-immune crosstalk in CNS diseases
    M Kerschensteiner
    Institute of Clinical Neuroimmunology, Ludwig Maximilians University Munich, Marchioninistr 17, 81377 Munich, Germany
    Neuroscience 158:1122-32. 2009
    ..It is thus the balance between destructive and protective factors that ultimately determines the net result of the neuro-immune interaction...
  95. pmc Redox proteomics analyses of the influence of co-expression of wild-type or mutated LRRK2 and Tau on C. elegans protein expression and oxidative modification: relevance to Parkinson disease
    Fabio Di Domenico
    Department of Chemistry, Center of Membrane Sciences, and Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA
    Antioxid Redox Signal 17:1490-506. 2012
    ..Expression and redox proteomics were used to identify the effects of LRRK2 (WT and mutant) on protein expression and oxidative modifications...
  96. ncbi Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease
    Pavan K Auluck
    Department of Neuroscience, University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 295:865-8. 2002
    ..Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinson's disease progression...
  97. pmc Lowered cortistatin expression is an early event in the human diabetic retina and is associated with apoptosis and glial activation
    Esther Carrasco
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM, Instituto de Salut Carlos III ISCIII, Barcelona, Spain
    Mol Vis 14:1496-502. 2008
    ..Retinal neurodegeneration was assessed by measuring glial fibrilar acidic protein (GFAP) by confocal laser microscopy and counting the apoptotic TUNEL positive cells in which nuclear fragmentation as well as condensation were present...
  98. pmc Neurodegeneration-associated TDP-43 interacts with fragile X mental retardation protein (FMRP)/Staufen (STAU1) and regulates SIRT1 expression in neuronal cells
    Zhipeng Yu
    The Third Hospital, Peking University, Beijing 100191, China
    J Biol Chem 287:22560-72. 2012
    ..Collectively, our results revealed a molecular mechanism for the cellular function of TDP-43 and might shed new light on the understanding of the mechanistic role of TDP-43 in neurodegenerative diseases...
  99. ncbi Cytokines and acute neurodegeneration
    S M Allan
    School of Biological Sciences, University of Manchester, 1 124 Stopford Building, Oxford Road, Manchester M13 9PT, UK
    Nat Rev Neurosci 2:734-44. 2001
    ..Understanding cytokine action in acute neurodegeneration could lead to novel and effective therapeutic strategies, some of which are already in clinical trials...
  100. ncbi Pael-R transgenic mice crossed with parkin deficient mice displayed progressive and selective catecholaminergic neuronal loss
    Hua Qin Wang
    Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan
    J Neurochem 107:171-85. 2008
    ..parkin-ko/Pael-R-tg mice represents an AR-JP mouse model displaying chronic and selective loss of catecholaminergic neurons...
  101. ncbi The brain as a target of inflammation: common pathways link inflammatory and neurodegenerative diseases
    Frauke Zipp
    Institute of Neuroimmunology, Charite Universitatsmedizin Berlin, 10098 Berlin, Germany
    Trends Neurosci 29:518-27. 2006
    ..Despite differing initial events, increasing evidence indicates that even in clinically heterogeneous diseases, there might be common immunological pathways that result in neurotoxicity and reveal targets for more efficient therapies...

Research Grants63

  1. Identification of Compounds to treat Charcot-Marie-Tooth type 2E neuropathy
    RONALD K LIEM; Fiscal Year: 2010
    ..The nerve degeneration causes the subsequent degeneration of the muscles in the extremities...
  2. Ca Signaling in Progression of Amyotrophic Lateral Sclerosis in Skeletal Muscle
    Jingsong Zhou; Fiscal Year: 2013
    ..It is generally believed nerve degeneration precedes and then causes the muscle atrophy...
  3. Experimental Optic Neuritis: Gene Therapy
    John Guy; Fiscal Year: 2011
    ..These novel findings implicate mitochondrial ROS activity as a key event in the initiation of optic nerve degeneration and demyelination in EAE...
  4. Mitochondrial Inborn Errors in Metabolism
    Douglas C Wallace; Fiscal Year: 2013
    ..LHON complex I gene mutations result in progressive retinal ganglion cell (RGC) and optic nerve degeneration with males being 2 to 5 times more likely to be affected than females and with a highly variable penetrance...
  5. Auditory Nerve Degeneration and Repair
    Hainan Lang; Fiscal Year: 2013
    ..In addition, information obtained will be of great public health interest for the design of therapeutic strategies for SNHL and other neurodegenerative disorders using glial cells as targets. ..
  6. A New Device for Rapid Measurement of Touch Sensation in neuropathy
    Donald A Simone; Fiscal Year: 2010
    ..in the disease process, when potential for recovery is greatest and to initiate therapy to prevent or slow nerve degeneration. In neuropathy, sensory dysfunction almost always begins in the distal extremities (fingers or toes) where ..
  7. The Role of Perineurial Glia in PNS Regeneration
    GWENDOLYN LEWIS; Fiscal Year: 2013
    ..axonal material, and 3) Using genetic manipulation to determine if perineurial glia are essential for nerve degeneration and regeneration...
  8. Inflammation and Degeneration of Optic Nerve in EAE
    Naren L Banik; Fiscal Year: 2013
    ..Understanding the pathophysiology of optic nerve degeneration in EAE has potential therapeutic implications to develop agents that restore visual function...
  9. Immunopathogenic mechanisms of dry eye disease
    Reza Dana; Fiscal Year: 2013
    ..and dysfunction are important aspects of DED, very little is understood about the mechanisms that effect nerve degeneration in DED...
  10. Caveolin-1 and Altered Neuregulinism in Diabetic Neuropathy
    Rick T Dobrowsky; Fiscal Year: 2012
    ..neuregulins in diabetic nerve from mice and to identify the molecular events by which neuregulins may induce nerve degeneration. The expected outcome of these studies is that we will identify molecular interactions that may enhance the ..
  11. Genetic analyses of axon transport and microtubule dynamics in Zebrafish
    Alex Nechiporuk; Fiscal Year: 2013
    ..consistent with defective axon transport and/or disrupted microtubule dynamics including: axon truncation, nerve degeneration and axonal swellings...
  12. A Device to Quantify Sweat of Single Sweat Glands to Diagnose Neuropathy
    William R Kennedy; Fiscal Year: 2013
    ..provide a better opportunity to treat, halt or reverse neuropathy than later discovery after significant nerve degeneration. Our sensitive sweat test (SST) detects early dysfunction of sudomotor nerves that activate sweat glands (..
  13. Studies of Retinopathy of AIDS in the HAART Era
    William R Freeman; Fiscal Year: 2013
    ..Optic nerve degeneration and apoptosis in tissue will also be evaluated...
  14. Non-Invasive Imaging to Quantify Peripheral Nerve Injury and Repair in Clinic
    Kazim A Sheikh; Fiscal Year: 2013
    ..for different peripheral nerves;and b) studies demonstrating utility of DTI technology to detect peripheral nerve degeneration and regeneration in humans...
  15. Local Mitochondrial Fusion in Myelinated Axons In Vivo
    Shing Yan Chiu; Fiscal Year: 2013
    ..Can we boost axons to use mitochondrial fusion as a defense to repair mitochondrial DNA damage and slow nerve degeneration in this disease that strikes ~ 1 in 10,000 adults in the US? PUBLIC HEALTH RELEVANCE: In this proposal, we ..
  16. The Bumps ad device for rapid non invasive quantification of touch sensation
    William R Kennedy; Fiscal Year: 2013
    ..a better chance to halt or reverse neuropathy than later discovery by tests that rely on the effects of nerve degeneration for diagnosis...
  17. A Device to Quantify Sweat of Single Sweat Glands to Diagnose Neuropathy
    William R Kennedy; Fiscal Year: 2011
    ..Early detection is beneficial because the potential for recovery declines with progressive nerve degeneration. Early diagnosis also provides the opportunity to decide if the chemotherapeutic agent should be decreased ..
  18. ShH10-Mediated Long-Term Delivery of Neurotrophic Factors in Animal Models of Gla
    Anna Maria Demetriades; Fiscal Year: 2013
    ..The hallmark of glaucoma is retinal ganglion cell (RGC) death, which leads to optic nerve degeneration and vision loss...
  19. Optic nerve regeneration: gene networks in retina development
    William H Klein; Fiscal Year: 2013
    ..We have developed realistic genetic models for human optic nerve degeneration that will have ultimate use in stem cell replacement therapy to repair damaged optic nerves.
  20. Manipulating retinal progenitor cells
    William H Klein; Fiscal Year: 2010
    ..of retinal development as well as establishing new approaches to regenerate damaged retinas and prevent or repair optic nerve degeneration in retinal pathologies such as optic neuritis, ischemic optic neuropathy, and glaucoma.
  21. Exploring mechanisms of TDP-43 aggregation and disaggregation
    James Shorter; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: Several devastating diseases that are caused by nerve degeneration, including amyotrophic lateral sclerosis (ALS), have been unified by a common underlying theme: the clumping ..
  22. Cellular and molecular mechanisms of peripheral sensory neuron regeneration
    GEORGEANN S O apos BRIEN; Fiscal Year: 2010
    Peripheral nerve degeneration due to disease or trauma can result in serious disability from permanent weakness, numbness or chronic pain...
  23. Phase III Trial of Minocycline in ALS:I-Clinical Center
    Paul Gordon; Fiscal Year: 2007
    ..Loss of motor neurons in the brain and spinal cord of ALS patients causes the progressive symptoms. Motor nerve degeneration may result from a cascade of events including free radical toxicity, glutamate excitotoxicity and ..
  24. Phenotype MicroArray Analysis of Fastidious Pathogens
    Barry Bochner; Fiscal Year: 2004
    ..gastroenteritis, and rheumatoid arthritis, and also (with some strains) of an autoimmune induced peripheral nerve degeneration and paralysis - Guillain Barre syndrome). Cj and Hp are each genetically diverse...
  25. ROLE OF NEUREGULIN ON AXON/GLIA INTERACTIONS IN DIABETES
    TIMOTHY RAABE; Fiscal Year: 2000
    ..Our long-range goal is to understand how Schwann cells and neurons interact during the process of nerve degeneration and subsequent nerve regeneration under hyperglycemic conditions...
  26. Modulators of CL-dependent Transport Processes (RMI)
    Eric Delpire; Fiscal Year: 2005
    ..cation-chloride co-transporters are responsible for diseases such as salt wasting disorders and peripheral nerve degeneration. They are also possibly involved in hypertension, age-related loss of hearing, neurological and psychiatric ..
  27. SYMPATHETIC NERVE REMODELING IN THE ADULT UTERUS
    Peter Smith; Fiscal Year: 2003
    ..rising plasma estrogen suppresses uterine neurotrophic factor production resulting in clinical sympathetic nerve degeneration followed by regeneration...
  28. PATHOGENESIS AND TREATMENT OF NERVE BLOCK INJURIES
    Robert Myers; Fiscal Year: 2006
    unreadable] DESCRIPTION (provided by applicant): Injury can initiate a painful process of nerve degeneration involving axons and their supporting Schwann cells (Wallerian degeneration) that is followed by a period of endoneurial ..
  29. Role of Acid-Sensing Ion Channels in Glaucoma
    Julie Saugstad; Fiscal Year: 2006
    Glaucoma comprises a group of ocular disorders that exhibit characteristic optic nerve degeneration (glaucomatous optic neuropathy, GON), associated with concomitant visual field loss, and often, increased intraocular pressure (lOP)...
  30. Molecular Determinants of Mitochondrial Optic Atrophy
    SUSAN CLINE; Fiscal Year: 2005
    ..LHON patients exhibit optic atrophy due to degeneration of the retinal ganglion cells, followed by optic nerve degeneration. Autosomal dominant optic (DOA) atrophy shares clinical and neuropathologic features with LHON...
  31. CENTRAL & PERIPHERAL EFFECT OF VINBLASTINE & VINCRISTINE
    SHARON COREY; Fiscal Year: 1980
    ..The effects of chronic doses on the development of sympathetic nerve degeneration in the rat are being assessed by measuring endogenous norepinephrine levels in various tissues, the ..
  32. OPA1 Mutation and Retinal Ganglion Cell Degeneration
    Ella Bossy Wetzel; Fiscal Year: 2009
    ..The goal of this project is to identify the mechanism underlying retinal ganglion cell and optic nerve degeneration in DOA...
  33. In Vivo Measurement of Optic Nerve Axon Loss
    JAMES LINDSEY; Fiscal Year: 2007
    ..optic nerve axon projections to the brain in mouse models of ocular disease characterized by gradual optic nerve degeneration. Aim 1...
  34. Targeting mitochondrial gene expression in the retina
    Alfred Lewin; Fiscal Year: 2009
    ..transfer of ribozymes, to create animal models with a common feature of many mitochondrial diseases - optic nerve degeneration. Ribozymes specific for a nucleus-encoded subunit (NDUFA1) of Complex I of the mitochondrial respiratory ..
  35. ENZYMATIC DE-INHIBITION OF AXONAL REGENERATION
    David Muir; Fiscal Year: 2003
    ..the neurite-promoting potentials of nerve and spinal cord; b) enzymatic inactivation of CSPG occurs during nerve degeneration; c) inactivation of CSPG during nerve degeneration is MMP-2-dependent and neuronal expression of MMP-2 ..
  36. Adenosine Agonists: Potential Antiglaucoma Agents
    Craig E Crosson; Fiscal Year: 2010
    ..of diseases affecting 2% of Americans over the age of 40 and is characterized by visual field loss and optic nerve degeneration. The long-term goals of this program are to understand the intrinsic mechanisms that regulate intraocular ..
  37. MOLECULAR BIOLOGY CORE INSTRUMENTATION FACILITY
    LAWRENCE CHASIN; Fiscal Year: 1991
    ..g. , oncogenes, tumor viruses, environmental mutagens, nerve degeneration) but for the most part they represent basic research in genetics, biochemistry, development, and neurobiology...
  38. Role of Persyn in Neurodegeneration
    Irina Surgucheva; Fiscal Year: 2003
    ..of persyn in glaucomatous alterations of the retina and optic nerve using: a) a pressure induced optic nerve degeneration model considered as one of the animal models of glaucoma and b) exploring the effect of elevated hydrostatic ..
  39. OCCUPATIONAL NEUROPATHIES DUE TO INDUSTRIAL CHEMICALS
    MOHAMED ABOU DONIA; Fiscal Year: 1992
    ..In the third section, we will investigate the possible role of the immune system on nerve degeneration that is observed after exposure to the chemicals which can covalently modify proteins, thus creating a ..
  40. Novel E3 Ligases in Nerve Degeneration and Regeneration
    Jeffrey Milbrandt; Fiscal Year: 2005
    ..In particular, the will focus our analysis on the processes of nerve degeneration/regeneration after mechanical and metabolic injury as well as synaptogenesis...
  41. Mechanisms of Motor Neuron Death
    Lee Martin; Fiscal Year: 2006
    ..abstract_text> ..
  42. MECHANISMS OF NEURONAL APOPTOSIS IN VIVO
    Lee Martin; Fiscal Year: 2009
    ..This work can define a new mitochondrial mechanism for target deprivation-induced neurodegeneration and can improve the understanding of the cellular and molecular mechanisms of neuronal apoptosis in vivo ..
  43. DNA Damage/Repair and Cell Death
    Lee Martin; Fiscal Year: 2009
    ....
  44. CASPASES, MITOCHONDRIAL FUNCTION AND PARKINSON'S DISEASE
    Anumantha Kanthasamy; Fiscal Year: 2006
    ..abstract_text> ..
  45. NEUROPROTECTIVE STRATEGIES AGAINST OXIDATIVE DAMAGE
    Anumantha Kanthasamy; Fiscal Year: 2009
    ....
  46. ETHANOL EFFECTS ON NEUROTRANSMISSION
    Fulton Crews; Fiscal Year: 2009
    ..abstract_text> ..
  47. Sphingolipids in Ethanol-Induced Neuronal Apoptosis
    Mariko Saito; Fiscal Year: 2010
    ..These studies will reveal the functions of sphingolipids in ethanol-induced apoptosis in the developing brain, and will offer bases for future therapeutic strategies for FASD. ..
  48. FAMILIAL PRIMARY OPEN ANGLE GLAUCOMA
    Janey Wiggs; Fiscal Year: 2004
    ..Initial genome screens to identify genes responsible for two POAG risk factors, ocular hypertension (OHT) and pseudoexfoliation (PEX), will be performed. ..
  49. HIV-1 protein neurotoxicity and ethanol pre-conditioning
    Michael Collins; Fiscal Year: 2006
    ..abstract_text> ..
  50. Antidepressants and Fibroblast Growth Factor
    Italo Mocchetti; Fiscal Year: 2006
    ..Data from this proposal may help elucidate the therapeutic efficacy of antidepressants in affective disorders. [unreadable] [unreadable]..
  51. THE PARKINSONIAN 6 HYDROXYDOPAMINE MODEL
    Charleen Chu; Fiscal Year: 2004
    ....
  52. Genetic Studies of Pseudoexfoliation Glaucoma
    Janey Wiggs; Fiscal Year: 2004
    ....
  53. 2005 Gordon Conference on Catecholamines
    David Sulzer; Fiscal Year: 2005
    ..abstract_text> ..
  54. FMRI/Pathology/Anterior Cingulate/Frontoinsular Cortex
    WILLIAM SEELEY; Fiscal Year: 2007
    ..The proposed research seeks to benefit the public health by clarifying the biological basis of dementia, ultimately promoting earlier diagnosis and better treatments for dementia patients. ..
  55. Training in proteomics of novel kinase substrates for neurodegeneration
    Charleen Chu; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  56. Cell survival and cell death in the auditory nerve
    Hainan Lang; Fiscal Year: 2008
    ..abstract_text> ..
  57. Reinnervation of Paralyzed Muscle by Nerve-Muscle-Endplate Band Grafting
    Liancai Mu; Fiscal Year: 2011
    ..Our preliminary work showed that this technique results in better outcomes than currently used methods. The data obtained from this research is useful for future clinical application to treat muscle paralysis. ..
  58. Calcium Homeostasis and Neonatal Brain Injury
    Christopher Turner; Fiscal Year: 2009
    ....
  59. Proteomic Analysis of Retinal Ganglion Cell Death in Glaucoma
    GULGUN TEZEL; Fiscal Year: 2010
    ..These studies are expected to provide comprehensive information about the nerve cell death process, thereby allowing new treatment possibilities for 3 million Americans suffering from glaucoma. ..
  60. Genetic Etiologies of Primary Open Angle Glaucoma
    Janey Wiggs; Fiscal Year: 2009
    ..Specific genetic defects will be correlated with clinical phenotype by investigating familial aggregation of clinical parameters and looking for evidence of gene/gene interactions and how these interactions may influence phenotype. ..
  61. Effect of Inducible Antioxidants on Hemoglobin Toxicity
    Raymond F Regan; Fiscal Year: 2010
    ..The ultimate goal is to reduce brain injury in tissue surrounding a blood clot, and to thereby improve the likelihood of survival and return to an independent, productive life. ..
  62. HIV Associated CNS Dysfunction with Aging
    Norman Haughey; Fiscal Year: 2007
    ..In vivo, we will test the protective effects of cholesterol reduction, inhibition of ceramide synthesis and reduction of oxidative stress in models of HIV protein-induced toxicity. ..