TorsinA and heat shock proteins act as molecular chaperones: suppression of α-synuclein aggregation
Article first published online: 4 NOV 2002
Journal of Neurochemistry
Volume 83, Issue 4, pages 846–854, November 2002
How to Cite
McLean, P. J., Kawamata, H., Shariff, S., Hewett, J., Sharma, N., Ueda, K., Breakefield, X. O. and Hyman, B. T. (2002), TorsinA and heat shock proteins act as molecular chaperones: suppression of α-synuclein aggregation. Journal of Neurochemistry, 83: 846–854. doi: 10.1046/j.1471-4159.2002.01190.x
- Issue published online: 4 NOV 2002
- Article first published online: 4 NOV 2002
- Received June 21, 2002; revised manuscript received August 2, 2002; accepted August 5, 2002.
- heat shock proteins;
- Lewy body;
- Parkinson's disease;
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 immunopositive 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.