Rho GTPases as therapeutic targets in Alzheimer's disease.
Rho GTPases as therapeutic targets in Alzheimer's disease.
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DOI：
10.1186/s13195-017-0320-4
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发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Lu Q
中科院分区：
文献类型：
--
作者：
Aguilar BJ;Zhu Y;Lu Q
我们在了解阿尔茨海默病（AD）发病机制方面取得的进展导致了一些新的途径和潜在的治疗靶点的确定。Rho GTPases被认为是AD发病机制的关键组成部分，但它们的各种功能和相互作用使得对其复杂信号传导的理解具有挑战性。在AD和Rho GTPase药物开发领域的最新进展为阐明Rho GTPases作为AD的可行靶点提供了新的工具。在此，我们总结了Rho gtpase在AD发病的各个阶段以及几种体外和体内AD模型中的波动活性。我们还回顾了目前用于靶向Rho gtpase的非甾体抗炎药、RhoA/ROCK、Rac1和Cdc42抑制剂及其在ad相关研究中的应用。最后，我们总结了几种AD小鼠模型中Rho GTPase调节后的行为改变。作为几种AD相关信号的关键调控因子，Rho GTPases被研究作为AD的靶点。然而，对于哪个阶段以Rho GTPases为目标最有利，尚未达成共识。本文讨论的研究强调了Rho GTPases的关键作用及其在AD中的调节作用。
The progress we have made in understanding Alzheimer’s disease (AD) pathogenesis has led to the identification of several novel pathways and potential therapeutic targets. Rho GTPases have been implicated as critical components in AD pathogenesis, but their various functions and interactions make understanding their complex signaling challenging to study. Recent advancements in both the field of AD and Rho GTPase drug development provide novel tools for the elucidation of Rho GTPases as a viable target for AD. Herein, we summarize the fluctuating activity of Rho GTPases in various stages of AD pathogenesis and in several in vitro and in vivo AD models. We also review the current pharmacological tools such as NSAIDs, RhoA/ROCK, Rac1, and Cdc42 inhibitors used to target Rho GTPases and their use in AD-related studies. Finally, we summarize the behavioral modifications following Rho GTPase modulation in several AD mouse models. As key regulators of several AD-related signals, Rho GTPases have been studied as targets in AD. However, a consensus has yet to be reached regarding the stage at which targeting Rho GTPases would be the most beneficial. The studies discussed herein emphasize the critical role of Rho GTPases and the benefits of their modulation in AD.
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