Alpha synuclein aggregation: is it the toxic gain of function responsible for neurodegeneration in Parkinson's disease?

Mech Ageing Dev. 2001 Sep 30;122(14):1499-510. doi: 10.1016/s0047-6374(01)00283-4.

Abstract

Protein aggregation appears to be the common denominator in a series of distinct neurodegenerative diseases yet its role in the associated neuronal pathology in these various conditions remains elusive. In Parkinson's disease, localization of alpha synuclein aggregates within intracellular Lewy body occlusions represent a major hallmark of this disorder and suggest that such aggregation may play a causative role in the resulting dopaminergic cell loss. In this Viewpoint article, recent data is reviewed related to how alpha synuclein aggregation may occur, what cellular events might be responsible, and how this may interfere with normal cellular function(s). It appears likely that while aggregation of alpha synuclein may interfere with its normal function in the cell, this is not the primary cause of the related neurodegeneration.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Synucleins
  • alpha-Synuclein

Substances

  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein