Synaptic Vulnerability in Neurodegenerative Disease

ABSTRACTRecent developments in our understanding of the pathophysiological mechanisms underlying degeneration in both the central and peripheral nervous systems have highlighted the critical role that synapses play in the instigation and progression of neuronal loss. In fact, several lines of eviden...

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Bibliographic Details
Published in:Journal of neuropathology and experimental neurology 2006-08, Vol.65 (8), p.733-739
Main Authors: Wishart, Thomas M, Parson, Simon H, Gillingwater, Thomas H
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Death - genetics
Central Nervous System - metabolism
Central Nervous System - pathology
Central Nervous System - physiopathology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Models, Animal
Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes
Genetic Predisposition to Disease - genetics
Humans
Medical sciences
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nervous system (semeiology, syndromes)
Neurodegenerative Diseases - genetics
Neurodegenerative Diseases - physiopathology
Neurodegenerative Diseases - therapy
Neurology
Presynaptic Terminals - metabolism
Presynaptic Terminals - pathology
Signal Transduction - genetics
Synapses - genetics
Synapses - metabolism
Synapses - pathology
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Summary:ABSTRACTRecent developments in our understanding of the pathophysiological mechanisms underlying degeneration in both the central and peripheral nervous systems have highlighted the critical role that synapses play in the instigation and progression of neuronal loss. In fact, several lines of evidence suggest that previous attempts to delay the onset and progression of clinical symptoms in a broad range of neurodegenerative diseases may have been unsuccessful as a result of a failure to protect synaptic compartments. As a result, the synapse needs to be viewed as an important target for the development of novel protective treatments aimed at preventing or slowing disease progression. We summarize important findings from human studies and animal models demonstrating common synaptic vulnerability across several neurodegenerative diseases. We also discuss recent developments in our understanding of degenerative mechanisms that are known to be localized to synapses and suggest potential ways to harness this understanding to develop synaptoprotective strategies for neurodegenerative disease.
ISSN:0022-3069
1554-6578
DOI:10.1097/01.jnen.0000228202.35163.c4