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 journalArticle

243 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
Externally publishedYes



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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

McLean, P. J., Kawamata, H., Shariff, S., Hewett, J., Sharma, N., Ueda, K., Breakefield, X. O., & Hyman, B. T. (2002). TorsinA and heat shock proteins act as molecular chaperones: Suppression of α-synuclein aggregation. Journal of Neurochemistry, 83(4), 846-854.