Synaptic vulnerability in neurodegenerative disease

Thomas M Wishart, Simon H Parson, Thomas H Gillingwater

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Recent 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.

Original languageEnglish
Pages (from-to)733-739
Number of pages7
JournalJournal of Neuropathology and Experimental Neurology
Volume65
Issue number8
DOIs
Publication statusPublished - Aug 2006

Keywords

  • Animals
  • Cell Death
  • Central Nervous System
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • Humans
  • Nerve Tissue Proteins
  • Neurodegenerative Diseases
  • Presynaptic Terminals
  • Signal Transduction
  • Synapses

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