Tauopathies: Deciphering Disease Mechanisms to Develop Effective Therapies.
Tauopathies: Deciphering Disease Mechanisms to Develop Effective Therapies.
复制标题
DOI：
10.3390/ijms21238948
复制
发表时间：
2020-11-25
影响因子：
5.6
通讯作者：
Haggarty SJ
中科院分区：
文献类型：
--
作者：
Silva MC;Haggarty SJ
tau蛋白病是神经退行性疾病，其特征在于微管相关蛋白tau（MAPT）以神经元缠结和成对螺旋丝的形式在神经元和神经胶质中病理性积累，导致脑细胞死亡。这些疾病包括额颞叶痴呆（FTD）和阿尔茨海默病（AD），并且当由MAPT基因突变引起时可以是散发性的或遗传性的。尽管全世界的社会经济负担非常高，但仍然没有有效的疾病修饰疗法，并且很少有以tau蛋白为重点的实验性药物进入临床试验。治疗开发的一个主要障碍是tau介导的神经元毒性和死亡的分子机制的知识缺口。为了实现对脑部疾病的精确医学的承诺，有必要整合已知的疾病遗传原因，即，MAPT突变，了解构成潜在治疗靶点的失调分子途径。在这里，不断增长的了解已知的和提出的疾病病因学机制将进行审查，连同有前途的实验tau定向治疗，如最近开发的tau降解剂。tau研究和药物发现领域目前面临的挑战也将得到解决。
Tauopathies are neurodegenerative diseases characterized by the pathological accumulation of microtubule-associated protein tau (MAPT) in the form of neurofibrillary tangles and paired helical filaments in neurons and glia, leading to brain cell death. These diseases include frontotemporal dementia (FTD) and Alzheimer’s disease (AD) and can be sporadic or inherited when caused by mutations in the MAPT gene. Despite an incredibly high socio-economic burden worldwide, there are still no effective disease-modifying therapies, and few tau-focused experimental drugs have reached clinical trials. One major hindrance for therapeutic development is the knowledge gap in molecular mechanisms of tau-mediated neuronal toxicity and death. For the promise of precision medicine for brain disorders to be fulfilled, it is necessary to integrate known genetic causes of disease, i.e., MAPT mutations, with an understanding of the dysregulated molecular pathways that constitute potential therapeutic targets. Here, the growing understanding of known and proposed mechanisms of disease etiology will be reviewed, together with promising experimental tau-directed therapeutics, such as recently developed tau degraders. Current challenges faced by the fields of tau research and drug discovery will also be addressed.
登录
查看更多内容
影响因子：
4.7
作者：
Babu, JR;Geetha, T;Wooten, MW
通讯作者：
Wooten, MW
影响因子：
16.6
作者：
Ambadipudi S;Biernat J;Riedel D;Mandelkow E;Zweckstetter M
通讯作者：
Zweckstetter M
影响因子：
14
作者：
通讯作者：
--
影响因子：
14.5
作者：
Arena, John D.;Smith, Douglas H.;Johnson, Victoria E.
通讯作者：
Johnson, Victoria E.
影响因子：
15.1
作者：
Bemiller SM;McCray TJ;Allan K;Formica SV;Xu G;Wilson G;Kokiko-Cochran ON;Crish SD;Lasagna-Reeves CA;Ransohoff RM;Landreth GE;Lamb BT
通讯作者：
Lamb BT