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药物重定位策略(DRS)在tau 病治疗中的潜在作用。

Potential role of Drug Repositioning Strategy (DRS) for management of tauopathy.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Horus University, New Damietta, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

出版信息

Life Sci. 2022 Feb 15;291:120267. doi: 10.1016/j.lfs.2021.120267. Epub 2021 Dec 30.

Abstract

Tauopathy is a term that has been used to represent a pathological condition in which hyperphosphorylated tau protein aggregates in neurons and glia which results in neurodegeneration, synapse loss and dysfunction and cognitive impairments. Recently, drug repositioning strategy (DRS) becomes a promising field and an alternative approach to advancing new treatments from actually developed and FDA approved drugs for an indication other than the indication it was originally intended for. This paradigm provides an advantage because the safety of the candidate compound has already been established, which abolishes the need for further preclinical safety testing and thus substantially reduces the time and cost involved in progressing of clinical trials. In the present review, we focused on correlation between tauopathy and common diseases as type 2 diabetes mellitus and the global virus COVID-19 and how tau pathology can aggravate development of these diseases in addition to how these diseases can be a risk factor for development of tauopathy. Moreover, correlation between COVID-19 and type 2 diabetes mellitus was also discussed. Therefore, repositioning of a drug in the daily clinical practice of patients to manage or prevent two or more diseases at the same time with lower side effects and drug-drug interactions is a promising idea. This review concluded the results of pre-clinical and clinical studies applied on antidiabetics, COVID-19 medications, antihypertensives, antidepressants and cholesterol lowering drugs for possible drug repositioning for management of tauopathy.

摘要

tau 病是一个术语,用于表示一种病理状态,其中过度磷酸化的 tau 蛋白在神经元和神经胶质中聚集,导致神经退行性变、突触丧失和功能障碍以及认知障碍。最近,药物重定位策略(DRS)成为一个有前途的领域和一种替代方法,从已经开发并获得 FDA 批准的药物中,为除了最初预期的适应症之外的适应症推进新的治疗方法。这种模式提供了一个优势,因为候选化合物的安全性已经得到了确立,从而消除了进一步进行临床前安全性测试的需要,因此大大减少了临床试验进展所涉及的时间和成本。在本综述中,我们重点关注 tau 病与 2 型糖尿病等常见疾病和全球病毒 COVID-19 之间的相关性,以及 tau 病理学如何加剧这些疾病的发展,以及这些疾病如何成为 tau 病发展的危险因素。此外,还讨论了 COVID-19 与 2 型糖尿病之间的相关性。因此,在患者的日常临床实践中重新定位一种药物,以同时管理或预防两种或更多疾病,同时降低副作用和药物相互作用,是一个有前途的想法。本综述总结了应用于抗糖尿病药物、COVID-19 药物、抗高血压药物、抗抑郁药物和降胆固醇药物的临床前和临床研究结果,以探讨可能用于 tau 病管理的药物重定位。

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