TorsinA and heat shock proteins act as molecular chaperones: suppression of alpha-synuclein aggregation. Academic Article uri icon

Overview

abstract

  • TorsinA, a protein with homology to yeast heat shock protein104, has previously been demonstrated to colocalize with alpha-synuclein in Lewy bodies, the pathological hallmark of Parkinson's disease. Heat shock proteins are a family of chaperones that are both constitutively expressed and induced by stressors, and that serve essential functions for protein refolding and/or degradation. Here, we demonstrate that, like torsinA, specific molecular chaperone heat shock proteins colocalize with alpha-synuclein in Lewy bodies. In addition, using a cellular model of alpha-synuclein aggregation, we demonstrate that torsinA and specific heat shock protein molecular chaperones colocalize with alpha-synuclein immunopositive inclusions. Further, overexpression of torsinA and specific heat shock proteins suppress alpha-synuclein aggregation in this cellular model, whereas mutant torsinA has no effect. These data suggest that torsinA has chaperone-like activity and that the disease-associated GAG deletion mutant has a loss-of-function phenotype. Moreover, these data support a role for chaperone proteins, including torsinA and heat shock proteins, in cellular responses to neurodegenerative inclusions.

publication date

  • November 1, 2002

Research

keywords

  • Carrier Proteins
  • Heat-Shock Proteins
  • Lewy Body Disease
  • Molecular Chaperones
  • Nerve Tissue Proteins

Identity

Scopus Document Identifier

  • 0036846119

Digital Object Identifier (DOI)

  • 10.1046/j.1471-4159.2002.01190.x

PubMed ID

  • 12421356

Additional Document Info

volume

  • 83

issue

  • 4