Alpha-synuclein mediates alterations in membrane conductance: a potential role for alpha-synuclein oligomers in cell vulnerability.
Alpha-synuclein mediates alterations in membrane conductance: a potential role for alpha-synuclein oligomers in cell vulnerability.
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DOI：
10.1111/j.1460-9568.2010.07266.x
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发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Maguire-Zeiss KA
中科院分区：
文献类型：
--
作者：
Feng LR;Federoff HJ;Vicini S;Maguire-Zeiss KA
α-突触核蛋白通过其形成毒性寡聚体的倾向与帕金森病和其他突触核蛋白病的发病机制有关。寡聚体突触核蛋白定向的细胞脆弱性的确切机制尚未完全阐明，但一种假设预示着细胞膜内形成含突触核蛋白的孔，导致泄漏通道介导的钙内流和随后的细胞死亡。在这里，我们证明了突触核蛋白诱导的SDS稳定的低聚物，细胞内突触核蛋白阳性聚集体，膜电导的改变，让人想起泄漏通道和随后的细胞毒性多巴胺能样细胞系的形成。此外，我们表明，突触核蛋白诱导的膜电导的变化被阻断直接细胞外应用的抗突触核蛋白抗体。这里提出的工作证实，突触核蛋白过表达导致膜电导的变化，并通过抗体阻断研究首次证明，突触核蛋白在渗漏通道的形成中起着直接的作用。
α-Synuclein has been linked to the pathogenesis of Parkinson's disease and other synucleinopathies through its propensity to form toxic oligomers. The exact mechanism for oligomeric synuclein-directed cell vulnerability has not been fully elucidated but one hypothesis portends the formation of synuclein-containing pores within cell membranes leading to leak channel-mediated calcium influx and subsequent cell death. Here we demonstrate synuclein-induced formation of SDS-stable oligomers, intracellular synuclein-positive aggregates, alterations in membrane conductance reminiscent of leak channels and subsequent cytotoxicity in a dopaminergic-like cell line. Furthermore we demonstrate that the synuclein-induced membrane conductance changes are blocked by direct extracellular application of an anti-synuclein antibody. The work presented here confirms that synuclein overexpression leads to membrane conductance changes and demonstrates for the first time through antibody blocking studies that synuclein plays a direct role in the formation of leak channels.
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影响因子：
82.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
4.7
作者：
Bellucci, Arianna;Collo, Ginetta;Spano, PierFranco
通讯作者：
Spano, PierFranco
影响因子：
3.8
作者：
Fornai, F;Lenzi, P;Paparelli, A
通讯作者：
Paparelli, A
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