Division of Biomedical Science and Biotechnology, School of Health Science, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
School of Pharmacy, Monash University Malaysia, 47500, Subang Jaya, Selangor, Malaysia.
Cell Mol Neurobiol. 2018 Jul;38(5):965-980. doi: 10.1007/s10571-017-0574-1. Epub 2018 Jan 3.
Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive function deficits. There are two major pathological hallmarks that contribute to the pathogenesis of AD which are the presence of extracellular amyloid plaques composed of amyloid-β (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Despite extensive research that has been done on Aβ in the last two decades, therapies targeting Aβ were not very fruitful at treating AD as the efficacy of Aβ therapies observed in animal models is not reflected in human clinical trials. Hence, tau-directed therapies have received tremendous attention as the potential treatments for AD. Tauopathies are closely correlated with dementia and immunotherapy has been effective at reducing tau pathology and improving cognitive deficits in animal models. Thus, in this review article, we discussed the pathological mechanism of tau proteins, the key factors contributing to tauopathies, and therapeutic approaches for tauopathies in AD based on the recent progress in tau-based research.
阿尔茨海默病(AD)的特征是进行性记忆丧失和认知功能缺陷。有两个主要的病理学特征导致 AD 的发病机制,即由淀粉样β(Aβ)组成的细胞外淀粉样斑块和由过度磷酸化 tau 组成的细胞内神经原纤维缠结。尽管在过去的二十年中对 Aβ 进行了广泛的研究,但针对 Aβ 的治疗方法在治疗 AD 方面并没有取得很大的成效,因为在动物模型中观察到的 Aβ 治疗效果并未在人类临床试验中得到体现。因此,tau 靶向治疗受到了极大的关注,作为 AD 的潜在治疗方法。tau 病与痴呆密切相关,免疫疗法在减少动物模型中的 tau 病理学和改善认知缺陷方面非常有效。因此,在这篇综述文章中,我们根据 tau 研究的最新进展,讨论了 tau 蛋白的病理机制、导致 tau 病的关键因素以及 AD 中 tau 病的治疗方法。