"Don't Phos Over Tau": recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer's disease and other tauopathies.
"Don't Phos Over Tau": recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer's disease and other tauopathies.
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“不要phos tau”：针对阿尔茨海默氏病和其他陶氏病的临床生物标志物和疗法的最新发展。
DOI：
10.1186/s13024-021-00460-5
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发表时间：
2021-06-05
影响因子：
15.1
通讯作者：
Giasson BI
中科院分区：
文献类型：
--
作者：
Xia Y;Prokop S;Giasson BI
磷酸化是从阿尔茨海默病(AD)患者脑中分离出来的聚集tau中发现的最普遍的翻译后修饰之一。在像AD这样的tau病中，磷酸化或过度磷酸化的增加可导致微管功能障碍，并与tau聚集有关。本文就tau蛋白的结构和功能以及tau蛋白磷酸化的生理作用作一综述。我们还广泛调查了AD患者脑组织和脑脊液中发现的tau磷酸化位点，并与年龄匹配的健康对照组进行了比较，这些位点可能作为疾病特异性生物标志物。最近，已经开发出新的检测方法来检测脑脊液和血浆中微量的特定形式的磷酸化tau，这可能有助于辅助临床诊断和监测疾病进展。此外，针对磷酸化tau的多种疗法正处于临床试验的不同阶段，包括激酶抑制剂、磷酸酶激活剂和tau免疫疗法。随着有希望的早期结果，靶向磷酸化tau蛋白的治疗方法可能有助于减缓AD和其他tau病的tau过度磷酸化和聚集。
Phosphorylation is one of the most prevalent post-translational modifications found in aggregated tau isolated from Alzheimer’s disease (AD) patient brains. In tauopathies like AD, increased phosphorylation or hyperphosphorylation can contribute to microtubule dysfunction and is associated with tau aggregation. In this review, we provide an overview of the structure and functions of tau protein as well as the physiologic roles of tau phosphorylation. We also extensively survey tau phosphorylation sites identified in brain tissue and cerebrospinal fluid from AD patients compared to age-matched healthy controls, which may serve as disease-specific biomarkers. Recently, new assays have been developed to measure minute amounts of specific forms of phosphorylated tau in both cerebrospinal fluid and plasma, which could potentially be useful for aiding clinical diagnosis and monitoring disease progression. Additionally, multiple therapies targeting phosphorylated tau are in various stages of clinical trials including kinase inhibitors, phosphatase activators, and tau immunotherapy. With promising early results, therapies that target phosphorylated tau could be useful at slowing tau hyperphosphorylation and aggregation in AD and other tauopathies.
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Tau通过调节动力蛋白和动力蛋白团队施加的力来指导细胞内贩运。
DOI：
10.1111/tra.12537
发表时间：
2018-03
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Chaudhary AR;Berger F;Berger CL;Hendricks AG
通讯作者：
Hendricks AG
影响因子：
14
作者：
通讯作者：
--
DOI：
10.1073/pnas.121119298
发表时间：
2001-06-05
影响因子：
11.1
作者：
Alonso, AD;Zaidi, T;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
4.6
作者：
Andersson, Christian Rungsted;Falsig, Jeppe;Pedersen, Jan Torleif
通讯作者：
Pedersen, Jan Torleif
影响因子：
12.7
作者：
Ahmed, Zeshan;Doherty, Karen M.;Revesz, Tamas
通讯作者：
Revesz, Tamas