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Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations

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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https://www.hal.inserm.fr/inserm-02439371
Contributor : Benjamin Dehay <>
Submitted on : Tuesday, January 14, 2020 - 3:45:11 PM
Last modification on : Thursday, November 12, 2020 - 9:30:16 AM

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Benjamin Dehay, Mathieu Bourdenx, Philippe Gorry, Serge Przedborski, Miquel Vila, et al.. Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations. The Lancet Neurology, Elsevier, 2015, 14 (8), pp.855-866. ⟨10.1016/S1474-4422(15)00006-X⟩. ⟨inserm-02439371⟩

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