The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Hsp70 Reduces α-Synuclein Aggregation and Toxicity
Open accessAbstract
Aggregation and cytotoxicity of misfolded alpha-synuclein is postulated to be crucial in the disease process of neurodegenerative disorders such as Parkinson's disease and DLB (dementia with Lewy bodies). In this study, we detected misfolded and aggregated alpha-synuclein in a Triton X-100 insoluble fraction as well as a high molecular weight product by gel electrophoresis of temporal neocortex from DLB patients but not from controls. We also found similar Triton X-100 insoluble forms of alpha-synuclein in an alpha-synuclein transgenic mouse model and in an in vitro model of alpha-synuclein aggregation. Introducing the molecular chaperone Hsp70 into the in vivo model by breeding alpha-synuclein transgenic mice with Hsp70-overexpressing mice led to a significant reduction in both the high molecular weight and detergent-insoluble alpha-synuclein species. Concomitantly, we found that Hsp70 overexpression in vitro similarly reduced detergent-insoluble alpha-synuclein species and protected cells from alpha-synuclein-induced cellular toxicity. Taken together, these data demonstrate that the molecular chaperone Hsp70 can reduce the amount of misfolded, aggregated alpha-synuclein species in vivo and in vitro and protect it from alpha-synuclein-dependent toxicity.
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The Role of Oxidative Stress in Parkinson's Disease
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-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
The HSP90 Family: Structure, Regulation, Function, and Implications in Health and Disease
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Telomeres: history, health, and hallmarks of aging
Chakravarti, D., LaBella, K. A., & DePinho, R. A. (2021) · Cell · doi:10.1016/j.cell.2020.12.028 · Cited by 637
α-Synuclein misfolding and aggregation: Implications in Parkinson’s disease pathogenesis
Mehra, S., Sahay, S., & Maji, S. K. (2019) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2019.03.001 · Cited by 499
Metadata
- Authors
- Klucken, J., Shin, Y., Masliah, E., Hyman, B. T., & McLean, P. J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 279
- Issue
- 24
- Pages
- 25497-25502
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2091586455
- Cited by
- 508
- References
- 67
- FWCI
- 16.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
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