期刊
LANCET NEUROLOGY
卷 14, 期 8, 页码 855-866出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S1474-4422(15)00006-X
关键词
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资金
- Fondation pour la Recherche Medicale
- Agence Nationale de la Recherche grants [ANR-12-BSV4-0001-01, LABEX BRAIN ANR-10-LABX-43]
- Intramural Research Program of the National Institute on Ageing, National Institutes of Health, Department of Health and Human Services project [ZO1 AG000949]
- Fondo de Investigacion Sanitaria-Instituto de Salud Carlos III, Spain
- Ministere de l'Enseignement Superieur et de la Recherche fellowship (France)
- Investissements d'avenir program [ANR-10-IAIHU-06]
- [ANR-13-BSV1-0013-01]
- ICREA Funding Source: Custom
Progressive neuronal cell loss in a small subset of brainstem and mesencephalic nuclei and widespread aggregation of the alpha-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 alpha-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 alpha-synuclein in the pathogenesis of Parkinson's disease has led researchers to consider the therapeutic potential of several strategies aimed at reduction of alpha-synuclein toxicity. We critically assess the potential of experimental therapies targeting alpha-synuclein, and discuss steps that need to be taken for target validation and drug development.
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