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Dehay, Benjamin, PhD; Bourdenx, Mathieu, MS; Gorry, Philippe, MD; Przedborski, Serge, Prof; Vila, Miquel, MD; Hunot, Stéphane, PhD; Singleton, Andrew, PhD; Olanow, C Warren, Prof; Merchant, Kalpana M, PhD; Bezard, Erwan, Prof; Petsko, Gregory A, Prof; Meissner, Wassilios G, Prof
Lancet neurology, 08/2015, Volume: 14, Issue: 8Journal Article
Summary 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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