The Cell Biology of Tau Secretion.
The Cell Biology of Tau Secretion.
复制标题
DOI：
10.3389/fnmol.2020.569818
复制
发表时间：
2020
影响因子：
4.8
通讯作者：
Huttunen HJ
中科院分区：
文献类型：
--
作者：
Merezhko M;Uronen RL;Huttunen HJ
错误折叠的tau蛋白在神经系统中的逐渐积累和扩散是tau病的标志，这是一种只能对症治疗的进行性神经退行性疾病。越来越多的证据表明，tau病理的传播可以通过细胞间转移发生，包括病理形式的tau蛋白的分泌和内化，然后是受体细胞中正常tau蛋白的模板错误折叠。一些研究已经解决了tau分泌的细胞生物学机制。现在看来，细胞可以通过三种共存的途径分泌tau蛋白，而不是单一的机制：(1)通过质膜的易位；(2)膜细胞器分泌；(3)外泌体脱落。然而，这些途径在正常和病理tau蛋白分泌中的相对重要性仍然难以捉摸。此外，神经胶质细胞参与tau的繁殖，不同细胞类型的参与以及不同的分泌途径，使对tau病的朊病毒样繁殖的理解复杂化。是神经元活动中tau分泌的重要调节因子之一，但其与tau分泌的机制联系尚不清楚，可能涉及tau的三种分泌途径。本文综述了tau蛋白分泌领域的最新进展，重点介绍了tau蛋白分泌过程的细胞生物学方面，并讨论了神经元活动和胶质细胞在病理形式tau蛋白扩散中的作用。
The progressive accumulation and spread of misfolded tau protein in the nervous system is the hallmark of tauopathies, progressive neurodegenerative diseases with only symptomatic treatments available. A growing body of evidence suggests that spreading of tau pathology can occur via cell-to-cell transfer involving secretion and internalization of pathological forms of tau protein followed by templated misfolding of normal tau in recipient cells. Several studies have addressed the cell biological mechanisms of tau secretion. It now appears that instead of a single mechanism, cells can secrete tau via three coexisting pathways: (1) translocation through the plasma membrane; (2) membranous organelles-based secretion; and (3) ectosomal shedding. The relative importance of these pathways in the secretion of normal and pathological tau is still elusive, though. Moreover, glial cells contribute to tau propagation, and the involvement of different cell types, as well as different secretion pathways, complicates the understanding of prion-like propagation of tauopathy. One of the important regulators of tau secretion in neuronal activity, but its mechanistic connection to tau secretion remains unclear and may involve all three secretion pathways of tau. This review article summarizes recent advancements in the field of tau secretion with an emphasis on cell biological aspects of the secretion process and discusses the role of neuronal activity and glial cells in the spread of pathological forms of tau.
登录
查看更多内容
影响因子：
11.1
作者：
Agostini S;Ali H;Vardabasso C;Fittipaldi A;Tasciotti E;Cereseto A;Bugatti A;Rusnati M;Lusic M;Giacca M
通讯作者：
Giacca M
影响因子：
4
作者：
Baker, Sian;Polanco, Juan Carlos;Gotz, Jurgen
通讯作者：
Gotz, Jurgen
DOI：
10.1073/pnas.121119298
发表时间：
2001-06-05
影响因子：
11.1
作者：
Alonso, AD;Zaidi, T;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
8.8
作者：
Calafate, Sara;Buist, Arjan;Moechars, Diederik
通讯作者：
Moechars, Diederik
影响因子：
64.8
作者：
CACERES, A;KOSIK, KS
通讯作者：
KOSIK, KS