Singh Sunidhi, Khan Sumaiya, Shahid Mohammad, Sardar Meryam, Hassan Md Imtaiyaz, Islam Asimul
Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Ageing Res Rev. 2025 Feb;104:102639. doi: 10.1016/j.arr.2024.102639. Epub 2024 Dec 16.
Tauopathies encompass a group of approximately 20 neurodegenerative diseases characterized by the accumulation of the microtubule-associated protein tau in brain neurons. The pathogenesis of intracellular neurofibrillary tangles, a hallmark of tauopathies, is initiated by hyperphosphorylated tau protein isoforms that cause neuronal death and lead to diseases like Alzheimer's, Parkinson's disease, frontotemporal dementia, and other complex neurodegenerative diseases. Current applications of tau biomarkers, including imaging, cerebrospinal fluid, and blood-based assays, assist in the evaluation and diagnosis of tauopathies. Emerging research is providing various potential strategies to prevent cellular toxicity caused by tau aggregation such as: 1) suppressing toxic tau aggregation, 2) preventing post-translational modifications of tau, 3) stabilizing microtubules and 4) designing tau-directed immunogens. This review aims to discuss the role of tau in tauopathies along with neuropathological features of the different tauopathies and the new developments in treating tau aggregation with the therapeutics for treating and possibly preventing tauopathies.
tau蛋白病是一组约20种神经退行性疾病，其特征是脑神经元中微管相关蛋白tau的积累。细胞内神经原纤维缠结是tau蛋白病的一个标志，其发病机制是由过度磷酸化的tau蛋白异构体引发的，这些异构体导致神经元死亡，并引发如阿尔茨海默病、帕金森病、额颞叶痴呆和其他复杂神经退行性疾病。目前tau生物标志物的应用，包括成像、脑脊液和基于血液的检测，有助于tau蛋白病的评估和诊断。新兴研究正在提供各种潜在策略来预防由tau聚集引起的细胞毒性，例如：1）抑制有毒tau聚集，2）防止tau的翻译后修饰，3）稳定微管，4）设计针对tau的免疫原。本综述旨在讨论tau在tau蛋白病中的作用，以及不同tau蛋白病的神经病理学特征，以及用治疗和可能预防tau蛋白病的疗法治疗tau聚集的新进展。
