a Department of Neurochemistry, Inge Grundke-Iqbal Research Floor , New York State Institute for Basic Research in Developmental Disabilities , Staten Island , NY , USA.
Expert Opin Drug Discov. 2018 May;13(5):399-410. doi: 10.1080/17460441.2018.1445084. Epub 2018 Mar 1.
Alzheimer's disease (AD), which accounts for three fourth of all cases of dementia, is a major public health problem in modern society and, yet, there is no effective treatment available that can prevent or inhibit this chronic progressive neurodegenerative disease. A major current drug target is intraneuronal abnormally hyperphosphorylated microtubule-associated protein tau which is a histopathological hallmark of this disease and of a family of neurodegenerative diseases called tauopathies. Areas covered: In this review, the authors discuss a growing number of studies that describe the nature and mechanism of tau pathology and various drug discovery options and most recent developments in tau-based therapeutics. PubMed was used to obtain relevant literature while clinicaltrials.gov site and Google search were employed to obtain the latest information on tau based AD clinical trials. Expert opinion: In authors' opinion, loss of neuronal connectivity leads to the hyperphosphorylation of tau and is thus a key therapeutic target. Rescue of neuronal connectivity loss and hyperphosphorylation of tau are most promising approaches. Consequently, tau immunotherapy has a high therapeutic potential.
阿尔茨海默病（AD）占所有痴呆症的四分之三，是现代社会的一个主要公共卫生问题，但目前尚无有效的治疗方法可以预防或抑制这种慢性进行性神经退行性疾病。目前的一个主要药物靶点是神经元内异常过度磷酸化的微管相关蛋白 tau，这是这种疾病和称为 tau 病的一类神经退行性疾病的组织病理学标志。
在这篇综述中，作者讨论了越来越多的描述 tau 病理学性质和机制以及各种药物发现选择和基于 tau 的治疗学最新进展的研究。作者使用 PubMed 获得相关文献，同时使用 clinicaltrials.gov 网站和 Google 搜索获取基于 tau 的 AD 临床试验的最新信息。
在作者看来，神经元连接的丧失导致 tau 的过度磷酸化，因此是一个关键的治疗靶点。挽救神经元连接的丧失和 tau 的过度磷酸化是最有前途的方法。因此，tau 免疫疗法具有很高的治疗潜力。
