Modulating the Amyloidogenesis of α-Synuclein.
Modulating the Amyloidogenesis of α-Synuclein.
复制标题
DOI：
10.2174/1570159x13666151030103153
复制
发表时间：
2016
影响因子：
5.3
通讯作者：
Andersen NH
中科院分区：
文献类型：
--
作者：
Sivanesam K;Andersen NH
α-突触核蛋白存在于神经元细胞中，但其天然功能尚不清楚。虽然 α-突触核蛋白是一种本质上无序的蛋白质，在膜结合时采用螺旋构象，但大量研究表明该蛋白质的寡聚 b 型具有细胞毒性。这种对错误折叠物种的反应导致了帕金森病的病因和症状。由此产生的淀粉样原纤维是帕金森病的既定诊断。在这篇综述中，我们重点关注通过稳定天然状态或将途径重定向到毒性较小的聚集体来抑制 α-突触核蛋白淀粉样蛋白生成的策略。多酚、肽等小分子以及大蛋白质已被证明可以有效保护细胞免受 α-突触核蛋白的细胞毒性。这些策略可能会导致治疗药物的开发，这些治疗药物可能有助于对抗这种疾病。
Alphα-synuclein is found in the neuronal cells but its native function is not well known. While α-synuclein is an intrinsically disordered protein that adopts a helical conformation upon membrane binding, numerous studies have shown that oligomeric b-forms of this protein are cytotoxic. This response to misfolded species contributes to Parkinson’s Disease etiology and symptoms. The resulting amyloid fibrils are an established diagnostic in Parkinson’s Disease. In this review, we focus on strategies that have been used to inhibit the amyloidogenesis of α-synuclein either by stabilizing the native state, or by redirecting the pathway to less toxic aggregates. Small molecules such as polyphenols, peptides as well as large proteins have proven effective at protecting cells against the cytotoxicity of α-synuclein. These strategies may lead to the development of therapeutic agents that could prove useful in combating this disease.