Hattiholi Aishwarya, Hegde Harsha, Shetty Suhas Kumar
Department of Ethnomedicine and Medicinal Plants/Plant Biotechnology, ICMR - National Institute of Traditional Medicine, Belagavi, Karnataka 590010, India; KLE Academy of Higher Education, Belagavi, Karnataka 590010, India.
Department of Ethnomedicine and Medicinal Plants/Plant Biotechnology, ICMR - National Institute of Traditional Medicine, Belagavi, Karnataka 590010, India.
Neuropeptides. 2025 Aug;112:102536. doi: 10.1016/j.npep.2025.102536. Epub 2025 Jul 2.
Tauopathies encompass a group of neurodegenerative disorders (NDDs) driven by the abnormal accumulation of mutated tau protein, leading to hyperphosphorylation, neuronal damage, and neuroinflammation. The protein plays essential roles in brain function but undergoes hyperphosphorylation and aggregation into toxic oligomers in NDDs. Recent research emphasizes the need to understand tau's post-translational modifications (PTMs) and their role in pathological states. Insights into tau's structure, isoform-specific properties, and aggregation mechanisms are critical for elucidating its propagation in neurodegeneration. Moreover, tau's potential as a biomarker and the development of targeted therapies to mitigate tauopathies, particularly in AD, remain promising avenues. However, many strategies targeted at tau have repeatedly failed, which continues the search for better alternatives. This review focuses on recent advances in tau research, highlighting its structural and functional characteristics, and roles in disease, that may be critical to understanding their implications for new therapeutic strategies. PTMs are important for the stable structure and physiological functions of a protein. However, dysfunctional PTMs are the leading causes of tau protein aggregation. The recent shift on tau hyperphosphorylation has resulted in many discoveries related to their functions in AD. Therapeutic strategies targeting phosphorylated tau are being extensively studied worldwide. This paper gives a comprehensive view on these aspects.
tau蛋白病是一组由突变tau蛋白异常积聚驱动的神经退行性疾病（NDDs），导致过度磷酸化、神经元损伤和神经炎症。该蛋白在脑功能中起重要作用，但在神经退行性疾病中会发生过度磷酸化并聚集成有毒的寡聚体。最近的研究强调需要了解tau蛋白的翻译后修饰（PTMs）及其在病理状态中的作用。深入了解tau蛋白的结构、异构体特异性特性和聚集机制对于阐明其在神经退行性变中的传播至关重要。此外，tau蛋白作为生物标志物的潜力以及开发减轻tau蛋白病（特别是在阿尔茨海默病中）的靶向治疗方法仍然是有前景的途径。然而，许多针对tau蛋白的策略屡屡失败，这促使人们继续寻找更好的替代方案。本综述重点关注tau蛋白研究的最新进展，突出其结构和功能特征以及在疾病中的作用，这些可能对理解其对新治疗策略的影响至关重要。翻译后修饰对于蛋白质的稳定结构和生理功能很重要。然而，功能失调的翻译后修饰是tau蛋白聚集的主要原因。最近对tau蛋白过度磷酸化的研究转变带来了许多与其在阿尔茨海默病中的功能相关的发现。针对磷酸化tau蛋白的治疗策略正在全球范围内广泛研究。本文对这些方面进行了全面阐述。
