Tauopathies: Emerging discoveries on tau protein, with a special focus on Alzheimer's disease

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides Pub Date : 2025-07-02 DOI:10.1016/j.npep.2025.102536

Aishwarya Hattiholi , Harsha Hegde , Suhas Kumar Shetty

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Abstract

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.

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tau病：关于tau蛋白的新发现，特别关注阿尔茨海默病

tau病包括一组由突变tau蛋白异常积累驱动的神经退行性疾病（ndd），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着至关重要的作用，但在ndd中会发生过度磷酸化并聚集成有毒的低聚物。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、亚型特异性和聚集机制对于阐明其在神经退行性疾病中的传播至关重要。此外，tau作为生物标志物的潜力和靶向治疗的发展，以减轻tau病变，特别是在AD中，仍然是有希望的途径。然而，许多针对tau蛋白的策略一再失败，这促使人们继续寻找更好的替代方案。本文综述了tau蛋白研究的最新进展，强调了其结构和功能特征，以及在疾病中的作用，这可能对理解它们对新的治疗策略的影响至关重要。PTMs对蛋白质的稳定结构和生理功能至关重要。然而，功能失调的ptm是tau蛋白聚集的主要原因。最近对tau过度磷酸化的转变导致了许多与其在AD中的功能相关的发现。针对磷酸化tau蛋白的治疗策略正在世界范围内被广泛研究。本文对这些方面进行了全面的论述。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.