Document Detail

Mechanisms underlying synaptic vulnerability and degeneration in neurodegenerative disease.
MedLine Citation:
PMID:  23289367     Owner:  NLM     Status:  Publisher    
Recent developments in our understanding of events underlying neurodegeneration across the central and peripheral nervous systems have highlighted the critical role that synapses play in the initiation and progression of neuronal loss. With the development of increasingly accurate and versatile animal models of neurodegenerative disease it has become apparent that disruption of synaptic form and function occurs comparatively early, preceding the onset of degenerative changes in the neuronal cell body. Yet, despite our increasing awareness of the importance of synapses in neurodegeneration, the mechanisms governing the particular susceptibility of distal neuronal processes are only now becoming clear. In this review we bring together recent developments in our understanding of cellular and molecular mechanisms regulating synaptic vulnerability. We have placed a particular focus on three major areas of research that have gained significant interest over the last few years: i) the contribution of synaptic mitochondria to neurodegeneration; ii) the contribution of pathways that modulate synaptic function; and, iii) regulation of synaptic degeneration by local post-translational modifications such as ubiquitination. We suggest that targeting these organelles and pathways may be a productive way to develop synaptoprotective strategies applicable to a range of neurodegenerative conditions.
Thomas H Gillingwater; Thomas M Wishart
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-7
Journal Detail:
Title:  Neuropathology and applied neurobiology     Volume:  -     ISSN:  1365-2990     ISO Abbreviation:  Neuropathol. Appl. Neurobiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7609829     Medline TA:  Neuropathol Appl Neurobiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 British Neuropathological Society.
Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK; Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh, Edinburgh, UK.
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