α-Synuclein Alters Toll-Like Receptor Expression.
α-Synuclein Alters Toll-Like Receptor Expression.
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DOI：
10.3389/fnins.2011.00080
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发表时间：
2011
影响因子：
4.3
通讯作者：
Maguire-Zeiss KA
中科院分区：
文献类型：
--
作者：
Béraud D;Twomey M;Bloom B;Mittereder A;Ton V;Neitzke K;Chasovskikh S;Mhyre TR;Maguire-Zeiss KA
帕金森病是一种与年龄相关的神经退行性疾病，其特征是黑质中多巴胺神经元的丢失，路易小体和神经突起中α-突触核蛋白的积聚，以及神经炎症。虽然散发性帕金森病的确切病因仍不清楚，但越来越多的证据表明，错误折叠的α-突触核蛋白促进炎症和氧化应激，导致神经退化。在体外，α-突触核蛋白直接与小胶质细胞的激活有关，在神经元丢失之前过度表达α-突触核蛋白的小鼠模型中，报道了激活的小胶质细胞数量增加。然而，α-突触核蛋白刺激小胶质细胞激活的机制还没有完全被描述。小胶质细胞的激活在一定程度上是由模式识别受体控制的，模式识别受体可以检测异物，并另外识别体内平衡细胞条件的变化。在启动促炎途径时，激活的小胶质细胞通过释放细胞因子、一氧化氮和其他活性氧物种来促进氧化应激，这可能会对邻近神经元产生不利影响。在这里，我们展示了小胶质细胞被α-突触核蛋白直接激活的经典激活途径，其中包括Toll样受体表达的变化。这些数据表明，α-突触核蛋白可以作为一种危险相关的分子模式。
Parkinson's disease, an age-related neurodegenerative disorder, is characterized by the loss of dopamine neurons in the substantia nigra, the accumulation of α-synuclein in Lewy bodies and neurites, and neuroinflammation. While the exact etiology of sporadic Parkinson's disease remains elusive, a growing body of evidence suggests that misfolded α-synuclein promotes inflammation and oxidative stress resulting in neurodegeneration. α-Synuclein has been directly linked to microglial activation in vitro and increased numbers of activated microglia have been reported in an α-synuclein overexpressing mouse model prior to neuronal loss. However, the mechanism by which α-synuclein incites microglial activation has not been fully described. Microglial activation is governed in part, by pattern recognition receptors that detect foreign material and additionally recognize changes in homeostatic cellular conditions. Upon proinflammatory pathway initiation, activated microglia contribute to oxidative stress through release of cytokines, nitric oxide, and other reactive oxygen species, which may adversely impact adjacent neurons. Here we show that microglia are directly activated by α-synuclein in a classical activation pathway that includes alterations in the expression of toll-like receptors. These data suggest that α-synuclein can act as a danger-associated molecular pattern.
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影响因子：
82.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
CD36介导了对β-淀粉样蛋白的先天宿主反应。
影响因子：
15.3
作者：
El Khoury, JB;Moore, KJ;Means, TK;Leung, J;Terada, K;Toft, M;Freeman, MW;Luster, AD
通讯作者：
Luster, AD
影响因子：
4.7
作者：
Biasini, E;Fioriti, L;Forloni, G
通讯作者：
Forloni, G
影响因子：
2.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
56.9
作者：
Conway, KA;Rochet, JC;Lansbury, PT
通讯作者：
Lansbury, PT