Pharmacological Modulators of Small GTPases of Rho Family in Neurodegenerative Diseases.
Pharmacological Modulators of Small GTPases of Rho Family in Neurodegenerative Diseases.
复制标题
神经退行性疾病中Rho家族小的GTPases的药理学调节剂。
DOI：
10.3389/fncel.2021.661612
复制
发表时间：
2021
影响因子：
5.3
通讯作者：
Lu Q
中科院分区：
文献类型：
--
作者：
Guiler W;Koehler A;Boykin C;Lu Q
经典的Rho GTPase，包括RhoA， Rac1和Cdc42，是Ras小GTPase超家族的成员，在多种细胞功能中发挥重要作用。Rho GTPase信号可以分别通过特定的gef和gap打开和关闭。这些特性使Rho GTPases及其上游和下游调节剂成为科学研究和治疗干预的目标。具体来说，由于Rho gtpase在神经组织中广泛存在细胞活性和改变，因此在神经退行性疾病中靶向Rho gtpase存在显著的治疗潜力。本研究将探讨Rho gtpase在神经退行性疾病中的作用，重点是最近发现的药理调节剂的应用。小分子、非甾体抗炎药（NSAIDs）、天然产物和毒素在每一个经典Rho GTPase类别中都有令人兴奋的发展。将提供每个类别的简要概述，并在其应用程序中提供示例。关于Rho GTPases在各种疾病中的作用的文献[例如，阿尔茨海默病（AD），帕金森病（PD），肌萎缩侧索硬化症（ALS），额颞叶痴呆（FTD）和多发性硬化症（MS）]强调了针对Rho GTPases的独特而广泛的潜在治疗干预意义。显然，从Rho GTPases的药理学调节剂的发现中，有越来越多的关于治疗前景的知识用于管理和治疗这些疾病。这一进展还伴随着对复杂Rho GTPase调节的认识，其中靶向其信号传导可以改善发病机制的某些方面，同时在同一疾病模型中加剧其他方面。未来的方向应该强调阐明不同Rho gtpase如何协同工作以及它们如何在神经退行性疾病进展中产生如此广泛但不同的细胞反应的重要性。
Classical Rho GTPases, including RhoA, Rac1, and Cdc42, are members of the Ras small GTPase superfamily and play essential roles in a variety of cellular functions. Rho GTPase signaling can be turned on and off by specific GEFs and GAPs, respectively. These features empower Rho GTPases and their upstream and downstream modulators as targets for scientific research and therapeutic intervention. Specifically, significant therapeutic potential exists for targeting Rho GTPases in neurodegenerative diseases due to their widespread cellular activity and alterations in neural tissues. This study will explore the roles of Rho GTPases in neurodegenerative diseases with focus on the applications of pharmacological modulators in recent discoveries. There have been exciting developments of small molecules, nonsteroidal anti-inflammatory drugs (NSAIDs), and natural products and toxins for each classical Rho GTPase category. A brief overview of each category followed by examples in their applications will be provided. The literature on their roles in various diseases [e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Frontotemporal dementia (FTD), and Multiple sclerosis (MS)] highlights the unique and broad implications targeting Rho GTPases for potential therapeutic intervention. Clearly, there is increasing knowledge of therapeutic promise from the discovery of pharmacological modulators of Rho GTPases for managing and treating these conditions. The progress is also accompanied by the recognition of complex Rho GTPase modulation where targeting its signaling can improve some aspects of pathogenesis while exacerbating others in the same disease model. Future directions should emphasize the importance of elucidating how different Rho GTPases work in concert and how they produce such widespread yet different cellular responses during neurodegenerative disease progression.
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影响因子：
7.1
作者：
Borin M;Saraceno C;Catania M;Lorenzetto E;Pontelli V;Paterlini A;Fostinelli S;Avesani A;Di Fede G;Zanusso G;Benussi L;Binetti G;Zorzan S;Ghidoni R;Buffelli M;Bolognin S
通讯作者：
Bolognin S
影响因子：
5.3
作者：
D'Ambrosi N;Rossi S;Gerbino V;Cozzolino M
通讯作者：
Cozzolino M
DOI：
10.1016/s0140-6736(15)00461-4
发表时间：
2015-10-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Bang J;Spina S;Miller BL
通讯作者：
Miller BL
影响因子：
5.7
作者：
Breitenlechner, C;Gassel, M;Bossemeyer, D
通讯作者：
Bossemeyer, D
影响因子：
5.3
作者：
Cerri, Chiara;Fabbri, Alessia;Caleo, Matteo
通讯作者：
Caleo, Matteo