Misfolded α-synuclein and Toll-like receptors: therapeutic targets for Parkinson's disease.
Misfolded α-synuclein and Toll-like receptors: therapeutic targets for Parkinson's disease.
复制标题
DOI：
10.1016/s1353-8020(11)70008-6
复制
发表时间：
2012-01
影响因子：
4.1
通讯作者：
Maguire-Zeiss, Kathleen A
中科院分区：
文献类型：
--
作者：
Beraud, Dawn;Maguire-Zeiss, Kathleen A
帕金森病（PD）的典型特征是中脑多巴胺神经元的丧失、存在大的蛋白质α-突触核蛋白阳性细胞内包涵体、氧化修饰的分子和活化的小胶质细胞。散发性帕金森病的病因尚未完全清楚，但有几条证据表明，遗传易感性和环境毒物会聚在一起，以煽动病理-多击假说。与家族性和散发性PD相关的一个基因是SNCA，其编码蛋白质α-突触核蛋白，该蛋白质具有错误折叠成毒性部分的倾向。在这里，我们发现α-突触核蛋白直接激活小胶质细胞，刺激促炎分子的产生，并改变Toll样受体（TLR）的表达。我们讨论了α-突触核蛋白介导的TLR表达变化在PD中的作用以及改变这种反应的治疗潜力。
Parkinson’s disease (PD) is typified by the loss of midbrain dopamine neurons, the presence of large proteinaceous α-synuclein-positive intracellular inclusions, oxidatively modified molecules and activated microglia. The etiology of sporadic PD is not fully understood but several lines of evidence suggest that genetic vulnerability and environmental toxicants converge to incite pathology-the multiple hit hypothesis. One gene linked to both familial and sporadic PD is SNCA, which encodes for the protein α-synuclein that has a propensity to misfold into toxic moieties. Here we show that α-synuclein directly activates microglia inciting the production of proinflammatory molecules and altering the expression of Toll-like receptors (TLRs). We discuss the role for α-synuclein-directed TLR expression changes in PD and the therapeutic potential of modifying this response.