Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease

Science. 2002 Feb 1;295(5556):865-8. doi: 10.1126/science.1067389. Epub 2001 Dec 20.

Abstract

Parkinson's disease is a movement disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Dopaminergic neuronal loss also occurs in Drosophila melanogaster upon directed expression of alpha-synuclein, a protein implicated in the pathogenesis of Parkinson's disease and a major component of proteinaceous Lewy bodies. We report that directed expression of the molecular chaperone Hsp70 prevented dopaminergic neuronal loss associated with alpha-synuclein in Drosophila and that interference with endogenous chaperone activity accelerated alpha-synuclein toxicity. Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinson's disease progression.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Brain Chemistry
  • Disease Models, Animal*
  • Dopamine / metabolism
  • Drosophila Proteins*
  • Drosophila melanogaster* / genetics
  • Female
  • HSC70 Heat-Shock Proteins
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / analysis
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins / analysis
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Inclusion Bodies / chemistry
  • Inclusion Bodies / ultrastructure
  • Lewy Bodies / chemistry
  • Lewy Bodies / ultrastructure
  • Male
  • Nerve Degeneration
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Neurons / physiology*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Parkinsonian Disorders* / genetics
  • Parkinsonian Disorders* / metabolism
  • Parkinsonian Disorders* / pathology
  • Synucleins
  • Transgenes
  • alpha-Synuclein

Substances

  • Drosophila Proteins
  • HSC70 Heat-Shock Proteins
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Hsc70-4 protein, Drosophila
  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein
  • Dopamine