Therapeutic Targeting of Rab GTPases: Relevance for Alzheimer's Disease.

Therapeutic Targeting of Rab GTPases: Relevance for Alzheimer's Disease.
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DOI:
10.3390/biomedicines10051141
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发表时间:
2022-05-16
期刊:
影响因子:
4.7
通讯作者:
--
中科院分区:
工程技术3区
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--
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Rabs GTPases (Rabs)是在囊泡运输和膜运输中起重要作用的小蛋白。由于Rabs在囊泡运输的几个步骤中具有广泛的功能,Rabs与多种疾病的发病机制有关,包括癌症、糖尿病和多种神经退行性疾病。由于目前对神经退行性疾病的治疗相当有限,因此识别和验证新的治疗靶点(如Rabs)非常重要。这篇综述总结了概念验证研究,证明了在阿尔茨海默病(AD)的背景下,Rab gtpase的调节可以改善疾病相关的表型,并提供了Rab的药理学靶向的当前状态的概述。最后,我们还讨论了在人类治疗中靶向这些小蛋白的障碍和挑战,特别是在AD的背景下。
Rab GTPases (Rabs) are small proteins that play crucial roles in vesicle transport and membrane trafficking. Owing to their widespread functions in several steps of vesicle trafficking, Rabs have been implicated in the pathogenesis of several disorders, including cancer, diabetes, and multiple neurodegenerative diseases. As treatments for neurodegenerative conditions are currently rather limited, the identification and validation of novel therapeutic targets, such as Rabs, is of great importance. This review summarises proof-of-concept studies, demonstrating that modulation of Rab GTPases in the context of Alzheimer’s disease (AD) can ameliorate disease-related phenotypes, and provides an overview of the current state of the art for the pharmacological targeting of Rabs. Finally, we also discuss the barriers and challenges of therapeutically targeting these small proteins in humans, especially in the context of AD.
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