Cellular and pathological heterogeneity of primary tauopathies.
Cellular and pathological heterogeneity of primary tauopathies.
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DOI：
10.1186/s13024-021-00476-x
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发表时间：
2021-08-23
影响因子：
15.1
通讯作者：
Dickson DW
中科院分区：
文献类型：
--
作者：
Chung DC;Roemer S;Petrucelli L;Dickson DW
微管相关的蛋白质tau在神经元细胞和神经胶质细胞中显着聚集，在一系列神经退行性疾病中，共同称为tauopathies。有助于tau病理的传播。关于积累的主要tau同工型，例如，具有tau夹杂物的大脑区域和细胞类型的脆弱性tau夹杂物甚至在同一细胞类型中也可以差异很大，这表明每种tauopathy中的不同机制或不同的tau构象体。 Tauopathies挑战了我们对Tau播种和聚集背后的病理生理学的理解，以及我们在本综述中为AD和其他Tauopathies制定有效的治疗策略。对小鼠模型，晚期转录组学和冷冻电子显微镜（Cryo-EM）的实验研究类型特异性的tau病理学。
Microtubule-associated protein tau is abnormally aggregated in neuronal and glial cells in a range of neurodegenerative diseases that are collectively referred to as tauopathies. Multiple studies have suggested that pathological tau species may act as a seed that promotes aggregation of endogenous tau in naïve cells and contributes to propagation of tau pathology. While they share pathological tau aggregation as a common feature, tauopathies are distinct from one another with respect to predominant tau isoforms that accumulate and the selective vulnerability of brain regions and cell types that have tau inclusions. For instance, primary tauopathies present with glial tau pathology, while it is mostly neuronal in Alzheimer’s disease (AD). Also, morphologies of tau inclusions can greatly vary even within the same cell type, suggesting distinct mechanisms or distinct tau conformers in each tauopathy. Neuropathological heterogeneity across tauopathies challenges our understanding of pathophysiology behind tau seeding and aggregation, as well as our efforts to develop effective therapeutic strategies for AD and other tauopathies. In this review, we describe diverse neuropathological features of tau inclusions in neurodegenerative tauopathies and discuss what has been learned from experimental studies with mouse models, advanced transcriptomics, and cryo-electron microscopy (cryo-EM) on the biology underlying cell type-specific tau pathology.