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

240 Citations (Scopus)

Abstract

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
Volume83
Issue number4
DOIs
StatePublished - Nov 2002
Externally publishedYes

Fingerprint

Synucleins
Molecular Chaperones
Heat-Shock Proteins
Agglomeration
Lewy Bodies
Specific heat
Protein Refolding
Proteins
Yeast
Proteolysis
Parkinson Disease
Shock
Hot Temperature
Yeasts
Phenotype
Degradation

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

TorsinA and heat shock proteins act as molecular chaperones : Suppression of α-synuclein aggregation. / McLean, Pamela J; Kawamata, Hibiki; Shariff, Saadat; Hewett, Jeffrey; Sharma, Nutan; Ueda, Kenji; Breakefield, Xandra O.; Hyman, Bradley T.

In: Journal of Neurochemistry, Vol. 83, No. 4, 11.2002, p. 846-854.

Research output: Contribution to journalArticle

McLean, PJ, Kawamata, H, Shariff, S, Hewett, J, Sharma, N, Ueda, K, Breakefield, XO & Hyman, BT 2002, 'TorsinA and heat shock proteins act as molecular chaperones: Suppression of α-synuclein aggregation', Journal of Neurochemistry, vol. 83, no. 4, pp. 846-854. https://doi.org/10.1046/j.1471-4159.2002.01190.x
McLean, Pamela J ; Kawamata, Hibiki ; Shariff, Saadat ; Hewett, Jeffrey ; Sharma, Nutan ; Ueda, Kenji ; Breakefield, Xandra O. ; Hyman, Bradley T. / TorsinA and heat shock proteins act as molecular chaperones : Suppression of α-synuclein aggregation. In: Journal of Neurochemistry. 2002 ; Vol. 83, No. 4. pp. 846-854.
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