Abstract |
Progressive neuronal cell loss in a small subset of brainstem and mesencephalic nuclei and widespread aggregation of the α- synuclein protein in the form of Lewy bodies and Lewy neurites are neuropathological hallmarks of Parkinson's disease. Most cases occur sporadically, but mutations in several genes, including SNCA, which encodes α- synuclein, are associated with disease development. The discovery and development of therapeutic strategies to block cell death in Parkinson's disease has been limited by a lack of understanding of the mechanisms driving neurodegeneration. However, increasing evidence of multiple pivotal roles of α- synuclein in the pathogenesis of Parkinson's disease has led researchers to consider the therapeutic potential of several strategies aimed at reduction of α- synuclein toxicity. We critically assess the potential of experimental therapies targeting α- synuclein, and discuss steps that need to be taken for target validation and drug development.
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Authors | Benjamin Dehay, Mathieu Bourdenx, Philippe Gorry, Serge Przedborski, Miquel Vila, Stephane Hunot, Andrew Singleton, C Warren Olanow, Kalpana M Merchant, Erwan Bezard, Gregory A Petsko, Wassilios G Meissner |
Journal | The Lancet. Neurology
(Lancet Neurol)
Vol. 14
Issue 8
Pg. 855-866
(Aug 2015)
ISSN: 1474-4465 [Electronic] England |
PMID | 26050140
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Review)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
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Topics |
- Animals
- Drug Discovery
- Humans
- Parkinson Disease
(drug therapy, metabolism)
- alpha-Synuclein
(chemistry, genetics, metabolism)
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