D M Walsh

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint The role of cell-derived oligomers of Abeta in Alzheimer's disease and avenues for therapeutic intervention
    D M Walsh
    Laboratory for Neurodegenerative Research, Conway Institute, University College Dublin, Republic of Ireland
    Biochem Soc Trans 33:1087-90. 2005
  2. ncbi request reprint Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration
    Dominic M Walsh
    Department of Neurology, Harvard Medical School, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Protein Pept Lett 11:213-28. 2004
  3. ncbi request reprint Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition
    D M Walsh
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Biochem Soc Trans 30:552-7. 2002
  4. ncbi request reprint A de novo designed helix-turn-helix peptide forms nontoxic amyloid fibrils
    Y Fezoui
    Department of Neurology Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Struct Biol 7:1095-9. 2000
  5. pmc In vitro studies of amyloid beta-protein fibril assembly and toxicity provide clues to the aetiology of Flemish variant (Ala692-->Gly) Alzheimer's disease
    D M Walsh
    Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston MA 02115, USA
    Biochem J 355:869-77. 2001
  6. ncbi request reprint The APP family of proteins: similarities and differences
    D M Walsh
    Laboratory for Neurodegenerative Research, Conway Institute, University College Dublin, Republic of Ireland
    Biochem Soc Trans 35:416-20. 2007
  7. doi request reprint Aberrant protein structure and diseases of the brain
    A T Welzel
    Laboratory for Neurodegenerative Research, Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4, Republic of Ireland
    Ir J Med Sci 180:15-22. 2011
  8. ncbi request reprint Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation
    W Q Qiu
    Department of Neurology and Program in Neuroscience, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115 5716, USA
    J Biol Chem 273:32730-8. 1998
  9. ncbi request reprint Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-beta oligomers
    Matthew Townsend
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA, USA
    Ann Neurol 60:668-76. 2006
  10. ncbi request reprint The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease
    Ronit Sharon
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02215, USA
    Neuron 37:583-95. 2003

Collaborators

Detail Information

Publications32

  1. ncbi request reprint The role of cell-derived oligomers of Abeta in Alzheimer's disease and avenues for therapeutic intervention
    D M Walsh
    Laboratory for Neurodegenerative Research, Conway Institute, University College Dublin, Republic of Ireland
    Biochem Soc Trans 33:1087-90. 2005
    ..In each case, compounds capable of reducing oligomer production or antibodies that avidly bind Abeta oligomers also ameliorate the synaptotoxic effects of these natural, cell-derived oligomers...
  2. ncbi request reprint Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration
    Dominic M Walsh
    Department of Neurology, Harvard Medical School, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Protein Pept Lett 11:213-28. 2004
    ..With particular reference to AD and PD, we review recent evidence that soluble oligomers are the principal pathogenic species that drive neuronal dysfunction...
  3. ncbi request reprint Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition
    D M Walsh
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Biochem Soc Trans 30:552-7. 2002
    ....
  4. ncbi request reprint A de novo designed helix-turn-helix peptide forms nontoxic amyloid fibrils
    Y Fezoui
    Department of Neurology Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Struct Biol 7:1095-9. 2000
    ..These results suggest that the potential to form fibrils under physiologic conditions is not limited to those proteins associated with amyloidoses and that fibril formation alone is not predictive of cytotoxic activity...
  5. pmc In vitro studies of amyloid beta-protein fibril assembly and toxicity provide clues to the aetiology of Flemish variant (Ala692-->Gly) Alzheimer's disease
    D M Walsh
    Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston MA 02115, USA
    Biochem J 355:869-77. 2001
    ..Increased peptide solubility and assembly stability would favour formation of larger deposits and inhibit their elimination. In addition, increased concentrations of neurotoxic assemblies would accelerate neuronal injury and death...
  6. ncbi request reprint The APP family of proteins: similarities and differences
    D M Walsh
    Laboratory for Neurodegenerative Research, Conway Institute, University College Dublin, Republic of Ireland
    Biochem Soc Trans 35:416-20. 2007
    ..Here, we will review how knowledge of the similarities and differences between APP and the APLPs may prove useful for the development of novel disease-modifying therapeutics...
  7. doi request reprint Aberrant protein structure and diseases of the brain
    A T Welzel
    Laboratory for Neurodegenerative Research, Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4, Republic of Ireland
    Ir J Med Sci 180:15-22. 2011
    ..We also discuss possible mechanisms by which aberrant protein structures may mediate disease and the therapeutic opportunities this knowledge offers...
  8. ncbi request reprint Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation
    W Q Qiu
    Department of Neurology and Program in Neuroscience, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115 5716, USA
    J Biol Chem 273:32730-8. 1998
    ..We conclude that a principal protease capable of down-regulating the levels of secreted Abeta extracellularly is IDE...
  9. ncbi request reprint Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-beta oligomers
    Matthew Townsend
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA, USA
    Ann Neurol 60:668-76. 2006
    ..A particularly attractive therapeutic strategy is to selectively neutralize small, soluble Abeta oligomers that have recently been shown to mediate synaptic dysfunction...
  10. ncbi request reprint The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease
    Ronit Sharon
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02215, USA
    Neuron 37:583-95. 2003
    ..We conclude that alpha S interacts with PUFAs in vivo to promote the formation of highly soluble oligomers that precede the insoluble alpha S aggregates associated with neurodegeneration...
  11. ncbi request reprint Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway
    Ganesh M Shankar
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 27:2866-75. 2007
    ..Our approach provides a quantitative cellular model for elucidating the molecular basis of Abeta-induced neuronal dysfunction...
  12. ncbi request reprint Deciphering the molecular basis of memory failure in Alzheimer's disease
    Dominic M Walsh
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Neuron 44:181-93. 2004
    ..Accordingly, attempts to slow memory and cognitive loss by decreasing cerebral Abeta levels have entered human trials...
  13. pmc Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's diseases
    G Brent Irvine
    School of Medicine and Dentistry, The Queen s University of Belfast, Belfast, Northern Ireland
    Mol Med 14:451-64. 2008
    ..In this review, we discuss this theme as it relates to the two most common neurodegenerative conditions-Alzheimer's and Parkinson's diseases...
  14. pmc Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization
    Igor Klyubin
    Institute of Neuroscience and Department of Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland
    J Neurosci 28:4231-7. 2008
    ..Abeta monomer isolated from human CSF did not affect long-term potentiation. These results strongly support a strategy of passive immunization against soluble Abeta oligomers in early Alzheimer's disease...
  15. pmc Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory
    Ganesh M Shankar
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nat Med 14:837-42. 2008
    ..We conclude that soluble Abeta oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species...
  16. doi request reprint Soluble amyloid-beta peptides potently disrupt hippocampal synaptic plasticity in the absence of cerebrovascular dysfunction in vivo
    Neng Wei Hu
    Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland
    Brain 131:2414-24. 2008
    ..This strongly indicates that early cognitive deficits can be caused by soluble Abeta independently of deleterious effects on cerebrovascular dynamics...
  17. ncbi request reprint Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo
    Igor Klyubin
    Trinity College Institute of Neuroscience, Department of Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland
    Nat Med 11:556-61. 2005
    ....
  18. ncbi request reprint A beta oligomers - a decade of discovery
    Dominic M Walsh
    Laboratory for Neurodegenerative Research, The Conway Institute, University College Dublin, Belfield, Dublin, Republic of Ireland
    J Neurochem 101:1172-84. 2007
    ..Here we review recent progress in understanding the role of soluble oligomers in Alzheimer's disease...
  19. ncbi request reprint Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo
    Dominic M Walsh
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 416:535-9. 2002
    ....
  20. pmc Loss of neprilysin function promotes amyloid plaque formation and causes cerebral amyloid angiopathy
    Wesley Farris
    Center for Neurologic Diseases, Department of Neurology, Harvard Institutes of Medicine, Room 730, Boston, MA 02115, USA
    Am J Pathol 171:241-51. 2007
    ....
  21. pmc Substrate-targeting gamma-secretase modulators
    Thomas L Kukar
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Nature 453:925-9. 2008
    ..These data also demonstrate the existence and feasibility of 'substrate targeting' by small-molecule effectors of proteolytic enzymes, which if generally applicable may significantly broaden the current notion of 'druggable' targets...
  22. ncbi request reprint Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death
    Malcolm A Leissring
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Harvard Medical School, Boston, MA 02115, USA
    Neuron 40:1087-93. 2003
    ..Our findings demonstrate that chronic upregulation of Abeta-degrading proteases represents an efficacious therapeutic approach to combating Alzheimer-type pathology in vivo...
  23. ncbi request reprint Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host
    Melanie Meyer-Luehmann
    Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, D 72076 Tubingen, Germany
    Science 313:1781-4. 2006
    ..The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Abeta strains with varying biological activities reminiscent of prion strains...
  24. ncbi request reprint Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well a
    Qinwen Wang
    Department of Physiology and Pharmacology, Trinity College, Dublin 2, Ireland
    J Neurosci 24:3370-8. 2004
    ..These studies provide evidence that the Abeta-mediated inhibition of LTP induction involves stimulation of the kinases JNK, Cdk5, and p38 MAPK after the activation of both the Abeta receptor(s) and mGluR5...
  25. ncbi request reprint Soluble Arctic amyloid beta protein inhibits hippocampal long-term potentiation in vivo
    Igor Klyubin
    Trinity College Institute of Neuroscience, and Department of Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland
    Eur J Neurosci 19:2839-46. 2004
    ....
  26. ncbi request reprint Soluble oligomers for the diagnosis of neurodegenerative diseases
    Omar M A El-Agnaf
    Department of Biological Sciences, Lancaster University, Lancaster, UK
    Lancet Neurol 2:461-2. 2003
  27. ncbi request reprint Amyloid beta-protein induced electrophysiological changes are dependent on aggregation state: N-methyl-D-aspartate (NMDA) versus non-NMDA receptor/channel activation
    Chianping Ye
    Department of Medicine at Harvard Medical School, Division of Endocrinology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Neurosci Lett 366:320-5. 2004
    ..These findings suggest that PFs may activate neurons differently than fibrils and lend support to the hypothesis that pre-fibrillar assemblies of Abeta may play an important role in the development of AD-type synaptic deficits...
  28. ncbi request reprint Species-specific immune response to immunization with human versus rodent A beta peptide
    Timothy J Seabrook
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Neurobiol Aging 25:1141-51. 2004
    ..Therefore, immunizing APP-tg and non-tg mice with rodent A beta resulted in a species-specific humoral response with modest T cell reactivity...
  29. ncbi request reprint Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function
    James P Cleary
    Geriatric Research, Education and Clinical Center, Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA
    Nat Neurosci 8:79-84. 2005
    ....
  30. ncbi request reprint gamma-Secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins
    Dominic M Walsh
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Biochemistry 42:6664-73. 2003
    ....
  31. pmc Effects of secreted oligomers of amyloid beta-protein on hippocampal synaptic plasticity: a potent role for trimers
    Matthew Townsend
    Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Physiol 572:477-92. 2006
    ..We conclude that specific assemblies, particularly timers, of naturally secreted Abeta oligomers are potent and selective inhibitors of certain forms of hippocampal LTP...
  32. ncbi request reprint Certain inhibitors of synthetic amyloid beta-peptide (Abeta) fibrillogenesis block oligomerization of natural Abeta and thereby rescue long-term potentiation
    Dominic M Walsh
    Department of Neurology, Harvard Medical School, and Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115 5716, USA
    J Neurosci 25:2455-62. 2005
    ....