Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations. Issue 8 (August 2015)

• Record Type: Journal Article
• Authors: Dehay, Benjamin; Bourdenx, Mathieu; Gorry, Philippe; Przedborski, Serge; Vila, Miquel; Hunot, Stéphane; Singleton, Andrew; Olanow, C Warren; Merchant, Kalpana M; Bezard, Erwan; Petsko, Gregory A; Meissner, Wassilios G
• Is Part Of: Lancet neurology. Volume 14:Issue 8(2015:Aug.)
• Page Start: 855
• Page End: 866
• Publication Date: 2015-08
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Nervous System Diseases -- Periodicals; Neurologie -- Périodiques; Neurology; Electronic journals; Periodicals; 616.805
• DOI: 10.1016/S1474-4422(15)00006-X
• Languages: English
• ISSNs: 1474-4422

Abstract

<abstract abstract-type="author" id="ceab10"> <title id="cestitle10">Summary</title> <sec> <p id="spara110">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 <italic>SNCA</italic>, 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.</p> </sec> </abstract>