Cellular models of alpha-synuclein toxicity and aggregation.
Cellular models of alpha-synuclein toxicity and aggregation.
复制标题
突触核蛋白毒性和聚集的细胞模型。
DOI：
10.1111/jnc.14806
复制
发表时间：
2019-09
影响因子：
4.7
通讯作者：
McLean PJ
中科院分区：
文献类型：
--
作者：
Delenclos M;Burgess JD;Lamprokostopoulou A;Outeiro TF;Vekrellis K;McLean PJ
α-突触核蛋白(α-突触核蛋白)的错误折叠和聚集伴随着细胞毒性，是路易体相关疾病的特征，如帕金森氏病、路易体痴呆和多系统萎缩。虽然α-突触核蛋白在这些疾病的发病机制和疾病进展中起着关键作用，但α-突触核蛋白在这些疾病中的功能和引起神经毒性的分子机制仍不清楚。多年来，已经产生了许多模拟α-突触核蛋白病理的体外和体内实验模型，如寡聚、毒性和最近的神经元增殖。特别是，细胞模型对于我们理解疾病的致病过程至关重要，并有助于筛选能够调节α-突触核蛋白毒性的分子。在这里，我们回顾了基于α-突触核蛋白的细胞培养模型，这些模型再现了患者中受影响的神经元群体的一些特征，从基本的单细胞生物到哺乳动物细胞系和原代神经元，再到患者特定细胞系的尖端模型。这些被称为诱导多能干细胞(IPSCs)的重新编程细胞已经引起了人们的关注，因为它们紧密地复制了患者中发现的神经元的特征，并为机制研究提供了一个有价值的工具。我们还讨论了不同的细胞模型如何构成高通量筛选能够调节α-突触核蛋白毒性的分子并防止其传播的强大工具。
Misfolding and aggregation of alpha-synuclein (α-synuclein) with concomitant cytotoxicity is a hallmark of Lewy body related disorders such as Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Although it plays a pivotal role in pathogenesis and disease progression, the function of α-synuclein and the molecular mechanisms underlying α-synuclein-induced neurotoxicity in these diseases are still elusive. Many in vitro and in vivo experimental models mimicking α-synuclein pathology such as oligomerization, toxicity and more recently neuronal propagation have been generated over the years. In particular, cellular models have been crucial for our comprehension of the pathogenic process of the disease and are beneficial for screening of molecules capable of modulating α-synuclein toxicity. Here, we review α-synuclein based cell culture models that reproduce some features of the neuronal populations affected in patients, from basic unicellular organisms to mammalian cell lines and primary neurons, to the cutting edge models of patient-specific cell lines. These reprogrammed cells known as induced pluripotent stem cells (iPSCs) have garnered attention because they closely reproduce the characteristics of neurons found in patients and provide a valuable tool for mechanistic studies. We also discuss how different cell models may constitute powerful tools for high-throughput screening of molecules capable of modulating α-synuclein toxicity and prevention of its propagation.
登录
查看更多内容
影响因子：
5.3
作者：
Dryanovski, Dilyan I.;Guzman, Jaime N.;Surmeier, D. James
通讯作者：
Surmeier, D. James
影响因子：
3.6
作者：
Cobb MM;Ravisankar A;Skibinski G;Finkbeiner S
通讯作者：
Finkbeiner S
在两个人类神经干细胞系中神经元生理反应性的差异发展。
影响因子：
2.4
作者：
Donato, Roberta;Miljan, Erik A.;Hines, Susan J.;Aouabdi, Sihem;Pollock, Kenneth;Patel, Sara;Edwards, Frances A.;Sinden, John D.
通讯作者：
Sinden, John D.
影响因子：
15.1
作者：
Danzer KM;Kranich LR;Ruf WP;Cagsal-Getkin O;Winslow AR;Zhu L;Vanderburg CR;McLean PJ
通讯作者：
McLean PJ
影响因子：
64.8
作者：
通讯作者：
--