α-Synuclein and mitochondrial dysfunction in Parkinson's disease

Mol Neurobiol. 2013 Apr;47(2):587-97. doi: 10.1007/s12035-013-8394-x. Epub 2013 Jan 30.

Abstract

α-Synuclein (SNCA) is a substantive component of Lewy bodies, the pathological hallmark of Parkinson's disease (PD). The discovery and subsequent derivation of its role in PD has led to a suprising but fruitful convergence of the fields of biochemistry and molecular genetics. In particular, the manipulation of the cell lines of a number of forms of familial PD has implicated SNCA in distinct and diverse biochemical pathways related to its pathogenesis. This current and rapidly evolving concept indicates PD is a disease in which interacting pathways of oxidative stress, mitochondrial dysfunction and impaired regulation of protein turnover interact to cause dopaminergic cell dysfunction and death. SNCA has a central role in these processes and manipulation of its expression, degradation and aggregation appear to be promising neuroprotective therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Mitochondria / genetics
  • Mitochondria / pathology
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / pathology*
  • Oxidative Stress / physiology
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Protein Transport / physiology
  • Signal Transduction / physiology
  • alpha-Synuclein / genetics
  • alpha-Synuclein / physiology*

Substances

  • alpha-Synuclein