Garrison Institute on Aging, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, USA.
Pharmacology & Neuroscience Department, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, USA.
Drug Discov Today. 2019 Feb;24(2):616-623. doi: 10.1016/j.drudis.2018.11.005. Epub 2018 Nov 16.
Phosphorylated tau (P-tau) has received much attention in the field of Alzheimer's disease (AD), as a potential therapeutic target owing to its involvement with synaptic damage and neuronal dysfunction. The continuous failure of amyloid β (Aβ)-targeted therapeutics highlights the urgency to consider alternative therapeutic strategies for AD. The present review describes the latest developments in tau biology and function. It also explains abnormal interactions between P-tau with Aβ and the mitochondrial fission protein Drp1, leading to excessive mitochondrial fragmentation and synaptic damage in AD neurons. This article also addresses 3D pharmacophore-based drug models designed to treat patients with AD and other tauopathies.
磷酸化 tau（P-tau）在阿尔茨海默病（AD）领域受到广泛关注，作为一种潜在的治疗靶点，因为它与突触损伤和神经元功能障碍有关。淀粉样蛋白β（Aβ）靶向治疗的持续失败突显了考虑 AD 替代治疗策略的紧迫性。本综述描述了 tau 生物学和功能的最新进展。它还解释了 P-tau 与 Aβ和线粒体分裂蛋白 Drp1 之间异常相互作用，导致 AD 神经元中过度的线粒体碎片化和突触损伤。本文还讨论了基于 3D 药效团的药物模型，旨在治疗 AD 和其他 tau 病患者。
