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Published Online December 20, 2001
Science DOI: 10.1126/science.1067389

Reports

Submitted on October 24, 2001
Accepted on December 11, 2001

Chaperone Suppression of {alpha}-Synuclein Toxicity in a Drosophila Model for Parkinson's Disease

Pavan K. Auluck 1, H. Y. Edwin Chan 2, John Q. Trojanowski 3, Virginia M.-Y. Lee 3, Nancy M. Bonini 4*

1 Department of Neuroscience, University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
2 Department of Biology, University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
3 Center for Neurodegenerative Disease Research and Department of Pathology and Laboratory Medicine, University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
4 Department of Neuroscience, Department of Biology, Howard Hughes Medical Institute, University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

* To whom correspondence should be addressed. E-mail: nbonini{at}sas.upenn.edu.

Parkinson's disease is a movement disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Dopaminergic neuronal loss also occurs in Drosophila upon directed expression of {alpha}-synuclein, a protein implicated in the pathogenesis of Parkinson's disease and a major component of proteinaceous Lewy Bodies. We report that directed expression of the molecular chaperone Hsp70 prevented dopaminergic neuronal loss associated with {alpha}-synuclein in Drosophila and that interference with endogenous chaperone activity accelerated {alpha}-synuclein toxicity. Furthermore, Lewy Bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinson's disease progression.


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Y. C. Tsai, P. S. Fishman, N. V. Thakor, and G. A. Oyler (2003)
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   Abstract »    Full Text »    PDF »
alpha -Synuclein Overexpression Protects against Paraquat-Induced Neurodegeneration.
A. B. Manning-Bog, A. L. McCormack, M. G. Purisai, L. M. Bolin, and D. A. Di Monte (2003)
J. Neurosci. 23, 3095-3099
   Abstract »    Full Text »    PDF »
Genetic modifiers in human development and malformation syndromes, including chaperone proteins.
A. Slavotinek and L. G. Biesecker (2003)
Hum. Mol. Genet. 12, R45-50
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Genomic convergence: identifying candidate genes for Parkinson's disease by combining serial analysis of gene expression and genetic linkage.
M. A. Hauser, Y.-J. Li, S. Takeuchi, R. Walters, M. Noureddine, M. Maready, T. Darden, C. Hulette, E. Martin, E. Hauser, et al. (2003)
Hum. Mol. Genet. 12, 671-677
   Abstract »    Full Text »    PDF »
blue cheese Mutations Define a Novel, Conserved Gene Involved in Progressive Neural Degeneration.
K. D. Finley, P. T. Edeen, R. C. Cumming, M. D. Mardahl-Dumesnil, B. J. Taylor, M. H. Rodriguez, C. E. Hwang, M. Benedetti, and M. McKeown (2003)
J. Neurosci. 23, 1254-1264
   Abstract »    Full Text »    PDF »
Suppression of polyglutamine-induced protein aggregation in Caenorhabditis elegans by torsin proteins.
G. A. Caldwell, S. Cao, E. G. Sexton, C. C. Gelwix, J. P. Bevel, and K. A. Caldwell (2003)
Hum. Mol. Genet. 12, 307-319
   Abstract »    Full Text »    PDF »
Chaperones increase association of tau protein with microtubules.
F. Dou, W. J. Netzer, K. Tanemura, F. Li, F. U. Hartl, A. Takashima, G. K. Gouras, P. Greengard, and H. Xu (2003)
PNAS 100, 721-726
   Abstract »    Full Text »    PDF »
Characterization of Cytoplasmic alpha -Synuclein Aggregates. FIBRIL FORMATION IS TIGHTLY LINKED TO THE INCLUSION-FORMING PROCESS IN CELLS.
H.-J. Lee and S.-J. Lee (2002)
J. Biol. Chem. 277, 48976-48983
   Abstract »    Full Text »    PDF »
Golgi Fragmentation Occurs in the Cells with Prefibrillar alpha -Synuclein Aggregates and Precedes the Formation of Fibrillar Inclusion.
N. Gosavi, H.-J. Lee, J. S. Lee, S. Patel, and S.-J. Lee (2002)
J. Biol. Chem. 277, 48984-48992
   Abstract »    Full Text »    PDF »
Parkin Accumulation in Aggresomes Due to Proteasome Impairment.
E. Junn, S. S. Lee, U. T. Suhr, and M. M. Mouradian (2002)
J. Biol. Chem. 277, 47870-47877
   Abstract »    Full Text »    PDF »
Suppression of polyglutamine toxicity by a Drosophila homolog of myeloid leukemia factor 1.
P. Kazemi-Esfarjani and S. Benzer (2002)
Hum. Mol. Genet. 11, 2657-2672
   Abstract »    Full Text »    PDF »
The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditiselegans.
J. F. Morley, H. R. Brignull, J. J. Weyers, and R. I. Morimoto (2002)
PNAS 99, 10417-10422
   Abstract »    Full Text »    PDF »
Interaction of intracellular beta amyloid peptide with chaperone proteins.
V. Fonte, V. Kapulkin, A. Taft, A. Fluet, D. Friedman, and C. D. Link (2002)
PNAS 99, 9439-9444
   Abstract »    Full Text »    PDF »
Toxic Proteins in Neurodegenerative Disease.
J. P. Taylor, J. Hardy, and K. H. Fischbeck (2002)
Science 296, 1991-1995
   Abstract »    Full Text »    PDF »


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