Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations.
Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations.
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DOI：
10.1016/s1474-4422(15)00006-x
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Meissner WG
中科院分区：
文献类型：
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作者：
Dehay B;Bourdenx M;Gorry P;Przedborski S;Vila M;Hunot S;Singleton A;Olanow CW;Merchant KM;Bezard E;Petsko GA;Meissner WG
帕金森病的神经病理学特征是脑干和中脑核团中进行性神经元细胞丢失和α-突触核蛋白以路易小体和路易突起的形式广泛聚集。大多数病例是零星发生的，但包括α-突触核蛋白在内的几个基因的突变与疾病的发展有关。导致神经变性的机制尚不清楚，因此限制了旨在阻止神经元死亡的治疗策略。该综述描述了α-突触核蛋白在帕金森病发病机制中的主要作用的证据，以及目前正在开发的一些最有前途的基于α-突触核蛋白的治疗这种不可治愈的神经退行性疾病的策略。
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 α-synuclein, are associated with disease development. The mechanisms driving neurodegeneration remain unknown, hence limiting therapeutic strategies aimed at blocking neuronal death. This review describes current evidence for a predominant role of α-synuclein in the pathogenesis of PD, as well as some of the most promising α-synuclein-based strategies currently in development for this incurable neurodegenerative disorder.