Duggal Aryan, Mahindru Drishti, Baghel Kirti, Mehrotra Sanjana, Prajapati Vijay Kumar
Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India.
Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, Dhaula Kuan, New Delhi, India.
Adv Protein Chem Struct Biol. 2025;146:77-136. doi: 10.1016/bs.apcsb.2024.11.012. Epub 2025 May 12.
Tau protein, a critical element for neuronal structure, becomes pathogenic in numerous neurodegenerative diseases, particularly Alzheimer's disease and other tauopathies. Under normal conditions, tau stabilizes microtubules and supports essential cellular transport systems. However, in disease states, tau undergoes abnormal modifications-most notably hyperphosphorylation-causing it to detach from microtubules and aggregate into neurofibrillary tangles. These aggregates disrupt neuronal function, leading to progressive cognitive and motor deficits. This chapter provides a comprehensive overview of tau's structural properties, normal cellular roles, and the cascade of pathological changes that transform it into a neurotoxic agent. We examine current therapeutic strategies targeting tau, including efforts to inhibit its phosphorylation, prevent aggregation, and enhance its clearance from cells. Approaches such as kinase inhibitors, immunotherapies, and gene-based therapies are discussed in the context of their potential to halt or slow disease progression. Additionally, recent advancements in diagnostic tools-such as tau-specific PET imaging and blood biomarkers-are highlighted as transformative for early detection of the disease .
tau蛋白是神经元结构的关键要素,在众多神经退行性疾病中具有致病性,尤其是阿尔茨海默病和其他tau蛋白病。在正常情况下,tau蛋白可稳定微管并支持重要的细胞运输系统。然而,在疾病状态下,tau蛋白会发生异常修饰——最显著的是过度磷酸化——导致其从微管上脱离并聚集成神经原纤维缠结。这些聚集体破坏神经元功能,导致进行性认知和运动功能障碍。本章全面概述了tau蛋白的结构特性、正常细胞功能以及将其转变为神经毒性因子的一系列病理变化。我们研究了目前针对tau蛋白的治疗策略,包括抑制其磷酸化、防止聚集以及增强其从细胞中清除的努力。在激酶抑制剂、免疫疗法和基因疗法等方法阻止或减缓疾病进展的潜力方面进行了讨论。此外,诊断工具的最新进展,如tau蛋白特异性PET成像和血液生物标志物,被强调为对该疾病的早期检测具有变革性意义。