The Role of alpha-synuclein assembly and metabolism in the pathogenesis of Lewy body disease

J Mol Neurosci. 2004;24(3):343-52. doi: 10.1385/JMN:24:3:343.

Abstract

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are members of a family of disorders characterized by the presence of inclusion bodies, or Lewy bodies (LBs), filled with aggregates of alpha-synuclein. These diseases are a leading cause of movement disorders and dementia in the aging population, and it is crucial to understand the factors leading to the accumulation and assembly of these alpha-synuclein aggregates. Previous studies have uncovered much about the factors leading to aggregation and the mechanisms causing neurotoxicity of these inclusion bodies; however, little is known about factors that promote the degradation and prevent the aggregation of alpha-synuclein. The present article provides a review of recent efforts in the investigation of factors involved in alpha-synuclein metabolism and the mechanisms involved in preventing accumulation of alpha-synuclein and degrading this molecule. Understanding these processes might provide targets for the development of novel therapies for disorders such as DLB and PD.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiopathology
  • Humans
  • Lewy Bodies / genetics
  • Lewy Bodies / metabolism
  • Lewy Body Disease / genetics*
  • Lewy Body Disease / metabolism*
  • Lewy Body Disease / physiopathology
  • Models, Neurological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oxidative Stress / physiology
  • Proteasome Endopeptidase Complex / metabolism
  • Signal Transduction / physiology
  • Synucleins
  • Ubiquitin / metabolism
  • alpha-Synuclein

Substances

  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • Ubiquitin
  • alpha-Synuclein
  • Proteasome Endopeptidase Complex