• 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, and Wassilios G Meissner.
• Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France.
• Lancet Neurol. 2015 Aug 1; 14 (8): 855-866.

AbstractProgressive 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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