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星形胶质细胞在神经退行性变类朊病毒机制中的作用。

The role of astrocytes in prion-like mechanisms of neurodegeneration.

机构信息

Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.

The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.

出版信息

Brain. 2022 Mar 29;145(1):17-26. doi: 10.1093/brain/awab366.

Abstract

Accumulating evidence suggests that neurodegenerative diseases are not merely neuronal in nature but comprise multicellular involvement, with astrocytes emerging as key players. The pathomechanisms of several neurodegenerative diseases involve the deposition of misfolded protein aggregates in neurons that have characteristic prion-like behaviours such as template-directed seeding, intercellular propagation, distinct conformational strains and protein-mediated toxicity. The role of astrocytes in dealing with these pathological prion-like protein aggregates and whether their responses either protect from or conspire with the disease process is currently unclear. Here we review the existing literature implicating astrocytes in multiple neurodegenerative proteinopathies with a focus on prion-like behaviour in this context.

摘要

越来越多的证据表明,神经退行性疾病不仅仅是神经元性质的,还包括多细胞的参与,其中星形胶质细胞是关键的参与者。几种神经退行性疾病的发病机制涉及到错误折叠的蛋白质聚集体在神经元中的沉积,这些聚集体具有特征性的类朊病毒样行为,如模板指导的接种、细胞间传播、独特的构象应变和蛋白质介导的毒性。星形胶质细胞在处理这些病理性类朊病毒样蛋白质聚集体中的作用,以及它们的反应是保护还是与疾病进程共谋,目前还不清楚。在这里,我们回顾了现有的文献,这些文献表明星形胶质细胞参与了多种神经退行性蛋白病,重点是在这种情况下的类朊病毒样行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e60/8967097/f3210e2484ee/awab366f1.jpg

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