School of Chemical and Biotechnology, SASTRA Deemed-to-be-University, Thanjavur 613401, Tamil Nadu, India.
School of Chemical and Biotechnology, SASTRA Deemed-to-be-University, Thanjavur 613401, Tamil Nadu, India.
Int J Biol Macromol. 2020 Nov 15;163:1599-1617. doi: 10.1016/j.ijbiomac.2020.07.327. Epub 2020 Aug 9.
Alzheimer's disease (AD) is a prevalently found tauopathy characterized by memory loss and cognitive insufficiency. AD is an age-related neurodegenerative disease with two major hallmarks which includes extracellular amyloid plaques made of amyloid-β (Aβ) and intracellular neurofibrillary tangles of hyperphosphorylated tau. With population aging worldwide, there is an indispensable need for treatment strategies that can potentially manage this developing dementia. Despite broad researches on targeting Aβ in the past two decades, research findings on Aβ targeted therapeutics failed to prove efficacy in the treatment of AD. Tau protein with its extensive pathological role in several neurodegenerative diseases can be considered as a promising target candidate for developing therapeutic interventions. The abnormal hyperphosphorylation of tau plays detrimental pathological functions which ultimately lead to neurodegeneration. This review will divulge the importance of tau in AD pathogenesis, the interplay of Aβ and tau, the pathological functions of tau, and potential therapeutic strategies for an effective management of neuronal disorders.
阿尔茨海默病(AD)是一种普遍存在的tau 病,其特征是记忆丧失和认知功能不足。AD 是一种与年龄相关的神经退行性疾病,有两个主要特征,包括由淀粉样蛋白-β(Aβ)组成的细胞外淀粉样斑块和过度磷酸化 tau 的细胞内神经原纤维缠结。随着全球人口老龄化,非常需要能够潜在管理这种进行性痴呆的治疗策略。尽管过去二十年广泛研究了针对 Aβ 的靶向治疗,但针对 Aβ 的靶向治疗研究结果未能证明在 AD 治疗中的有效性。tau 蛋白在几种神经退行性疾病中具有广泛的病理作用,可以被认为是开发治疗干预措施的有前途的候选靶标。tau 的异常过度磷酸化发挥有害的病理功能,最终导致神经退行性变。本综述将揭示 tau 在 AD 发病机制中的重要性、Aβ 和 tau 的相互作用、tau 的病理功能以及有效管理神经元疾病的潜在治疗策略。