Microglia: Friend and foe in tauopathy.
Microglia: Friend and foe in tauopathy.
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DOI：
10.1016/j.pneurobio.2022.102306
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发表时间：
2022-09
影响因子：
6.7
通讯作者：
Hopp, Sarah C.
中科院分区：
文献类型：
--
作者：
Odfalk, Kristian F.;Bieniek, Kevin F.;Hopp, Sarah C.
错误折叠的微管相关蛋白tau聚集成异常的细胞内包涵体定义了一类称为tau蛋白病的神经退行性疾病。阿尔茨海默病（AD）中tau病理学的一致时空进展导致以下假设：tau聚集体通过生物活性tau“种子”在脑中扩散，这是疾病进程进展的基础。最近的研究表明，小胶质细胞，中枢神经系统的常驻免疫细胞，在负和正调节tau病理。改变小胶质细胞功能的基因多态性与AD和其他tau蛋白病的发展相关。小胶质细胞功能的实验操作可以改变tau病理学，并且小胶质细胞介导的神经炎症级联反应可以加剧tau病理学。小胶质细胞还通过减轻tau扩散发挥保护功能：小胶质细胞内化tau种子并具有降解它们的能力。然而，当小胶质细胞不能降解这些tau种子时，就会产生有害的后果，包括分泌含有tau的外泌体，这些外泌体可以扩散到神经元。本文从神经病理学、神经影像学、遗传学、转录组学和分子生物学的角度探讨了小胶质细胞和tau蛋白的交叉点。随着tau靶向治疗如抗tau抗体通过临床试验的进展，了解tau和小胶质细胞之间的相互作用至关重要。
Aggregation of misfolded microtubule associated protein tau into abnormal intracellular inclusions defines a class of neurodegenerative diseases known as tauopathies. The consistent spatiotemporal progression of tau pathology in Alzheimer’s disease (AD) led to the hypothesis that tau aggregates spread in the brain via bioactive tau “seeds” underlying advancing disease course. Recent studies implicate microglia, the resident immune cells of the central nervous system, in both negative and positive regulation of tau pathology. Polymorphisms in genes that alter microglial function are associated with the development of AD and other tauopathies. Experimental manipulation of microglia function can alter tau pathology and microglia-mediated neuroinflammatory cascades can exacerbate tau pathology. Microglia also exert protective functions by mitigating tau spread: microglia internalize tau seeds and have the capacity to degrade them. However, when microglia fail to degrade these tau seeds there are deleterious consequences, including secretion of exosomes containing tau that can spread to neurons. This review explores the intersection of microglia and tau from the perspective of neuropathology, neuroimaging, genetics, transcriptomics, and molecular biology. As tau-targeted therapies such as anti-tau antibodies advance through clinical trials, it is critical to understand the interaction between tau and microglia.
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影响因子：
16.2
作者：
Bhaskar, Kiran;Konerth, Megan;Kokiko-Cochran, Olga N.;Cardona, Astrid;Ransohoff, Richard M.;Lamb, Bruce T.
通讯作者：
Lamb, Bruce T.
影响因子：
12.7
作者：
Ando, Kunie;Brion, Jean-Pierre;Duyckaerts, Charles
通讯作者：
Duyckaerts, Charles
影响因子：
15.1
作者：
Bemiller SM;McCray TJ;Allan K;Formica SV;Xu G;Wilson G;Kokiko-Cochran ON;Crish SD;Lasagna-Reeves CA;Ransohoff RM;Landreth GE;Lamb BT
通讯作者：
Lamb BT
影响因子：
3.3
作者：
Bohdanowicz M;Schlam D;Hermansson M;Rizzuti D;Fairn GD;Ueyama T;Somerharju P;Du G;Grinstein S
通讯作者：
Grinstein S
影响因子：
25
作者：
Asai H;Ikezu S;Tsunoda S;Medalla M;Luebke J;Haydar T;Wolozin B;Butovsky O;Kügler S;Ikezu T
通讯作者：
Ikezu T