β-Synuclein Regulates Akt Activity in Neuronal Cells
β-Synuclein Regulates Akt Activity in Neuronal Cells
复制标题
β-突触核蛋白调节神经元细胞中的 Akt 活性
DOI：
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发表时间：
2004
影响因子：
4.8
通讯作者：
E. Masliah
中科院分区：
文献类型：
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作者：
M. Hashimoto;P. Bar;G. Ho;T. Takenouchi;E. Rockenstein;L. Crews;E. Masliah
最近的研究表明，路易体形成障碍（如帕金森病和路易体痴呆）的神经退行性过程与α-突触核蛋白蓄积有关，β-突触核蛋白可能保护中枢神经系统免受α-突触核蛋白的神经毒性作用。然而，其机制尚不清楚。本研究的主要目的是探讨丝氨酸苏氨酸激酶Akt（也称为蛋白激酶B）信号通路在β-突触核蛋白神经保护机制中的潜在参与。为此，Akt活性和细胞存活率进行了分析，在突触核蛋白转染的B103神经母细胞瘤细胞和原代皮质神经元。β-突触核蛋白转染导致Akt活性增加，并提供保护，免受鱼藤酮的神经毒性作用。Akt表达的下调导致对鱼藤酮毒性的易感性增加，而用编码β-突触核蛋白的慢病毒载体转染具有保护作用。β-突触核蛋白对Akt通路的影响似乎是通过这些分子之间的直接相互作用，并且不依赖于上游信号分子。总之，这些结果表明β-突触核蛋白神经保护的机制可能涉及β-突触核蛋白和Akt之间的直接相互作用，并表明该信号传导途径可能是与帕金森综合征和α-突触核蛋白聚集相关的神经系统疾病的潜在治疗靶点。
Recent studies have shown that the neurodegenerative process in disorders with Lewy body formation, such as Parkinson's disease and dementia with Lewy bodies, is associated with α-synuclein accumulation and that β-synuclein might protect the central nervous system from the neurotoxic effects of α-synuclein. However, the mechanisms are unclear. The main objective of the present study was to investigate the potential involvement of the serine threonine kinase Akt (also known as protein kinase B) signaling pathway in the mechanisms of β-synuclein neuroprotection. For this purpose, Akt activity and cell survival were analyzed in synuclein-transfected B103 neuroblastoma cells and primary cortical neurons. β-Synuclein transfection resulted in increased Akt activity and conferred protection from the neurotoxic effects of rotenone. Down-regulation of Akt expression resulted in an increased susceptibility to rotenone toxicity, whereas transfection with a lentiviral vector encoding for β-synuclein was protective. The effects of β-synuclein on the Akt pathway appear to be by direct interaction between these molecules and were independent of upstream signaling molecules. Taken together, these results indicate that the mechanisms of β-synuclein neuroprotection might involve direct interactions between β-synuclein and Akt and suggest that this signaling pathway could be a potential therapeutic target for neurological conditions associated with parkinsonism and α-synuclein aggregation.
蛋白酶 K 和甲酸预处理揭示了路易体病中阿尔茨海默病淀粉样蛋白前体/α-突触核蛋白的非 Abeta 成分的异常分布。
DOI：
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发表时间：
1998
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Takeda,A;Hashimoto,M;Mallory,M;Sundsumo,M;Hansen,L;Sisk,A;Masliah,E
通讯作者：
Masliah,E
影响因子：
56.9
作者：
Masliah, E;Rockenstein, E;Mucke, L
通讯作者：
Mucke, L
影响因子：
2.9
作者：
Jenco, JM;Rawlingson, A;Morris, AJ
通讯作者：
Morris, AJ