Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, UK.
UK-Dementia Research Institute, Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
Adv Exp Med Biol. 2019;1184:113-121. doi: 10.1007/978-981-32-9358-8_10.
It is well documented that tauopathy is involved in various forms of neurodegenerative disease. However, there is a huge gap in terms of our understanding of the neurophysiological roles of tau, and how these can be aberrantly regulated by pathological processes. Tau is enriched in the axon but is also localized to synapses. The finding of synaptically localised tau has undoubtedly created more questions than it has answered. What is the physiological role of tau at the synapse? Whether and how does tau interact with and effect other synaptic proteins to mediate this function? Are these effects regulated by post-translational modifications of tau, such as phosphorylation? Such questions require significant attention from the scientific community if we are to resolve this critical aspect of tau biology. This chapter will describe our current understanding of synaptic tau and its functions and illuminate the numerous remaining challenges in this evolving research area.
有大量文献记录表明，tau 病在各种形式的神经退行性疾病中都有涉及。然而，我们对 tau 的神经生理学作用及其如何被病理过程异常调节的理解还存在很大的差距。tau 在轴突中富集，但也定位于突触。突触定位 tau 的发现无疑提出了更多的问题，而不是回答了更多的问题。tau 在突触中的生理作用是什么？tau 是否以及如何与其他突触蛋白相互作用并影响其功能？这些影响是否受 tau 的翻译后修饰（如磷酸化）调节？如果我们要解决 tau 生物学的这一关键方面，科学界需要对这些问题给予高度关注。本章将描述我们目前对突触 tau 的理解及其功能，并阐明这一不断发展的研究领域中仍存在的许多挑战。
