TorsinA and heat shock proteins act as molecular chaperones: Suppression of α-synuclein aggregation

Pamela J. McLean, Hibiki Kawamata, Saadat Shariff, Jeffrey Hewett, Nutan Sharma, Kenji Ueda, Xandra O. Breakefield, Bradley T. Hyman

Research output: Contribution to journalArticlepeer-review

259 Scopus citations


TorsinA, a protein with homology to yeast heat shock protein104, has previously been demonstrated to colocalize with α-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 α-synuclein in Lewy bodies. In addition, using a cellular model of α-synuclein aggregation, we demonstrate that torsinA and specific heat shock protein molecular chaperones colocalize with α-synuclein immuno-positive inclusions. Further, overexpression of torsinA and specific heat shock proteins suppress α-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.

Original languageEnglish (US)
Pages (from-to)846-854
Number of pages9
JournalJournal of neurochemistry
Issue number4
StatePublished - Nov 2002


  • Aggregation
  • Heat shock proteins
  • Lewy body
  • Parkinson's disease
  • TorsinA
  • α-synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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