Rho GTPases as therapeutic targets in Alzheimer's disease

被引：84

作者：

Aguilar, Byron J. ^{[1
]}

Zhu, Yi ^{[1
]}

Lu, Qun ^{[1
,2
]}

机构：

[1] East Carolina Univ, Brody Sch Med, Dept Anat & Cell Biol, Greenville, NC 27834 USA

[2] East Carolina Univ, Brody Sch Med, Harriet & John Wooten Lab Alzheimers & Neurodegen, Greenville, NC 27834 USA

来源：

ALZHEIMERS RESEARCH & THERAPY | 2017年 / 9卷

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; Rho GTPases; Cdc42; Rac1; RhoA; NSAIDs; AD mouse model; AD therapy; AMYLOID PRECURSOR PROTEIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GAMMA-SECRETASE; A-BETA; NECROTIZING FACTOR; SIGNALING PATHWAY; MITOCHONDRIAL DYSFUNCTION; SYNAPTIC PLASTICITY; COGNITIVE DEFICITS; ROCK INHIBITORS;

D O I：

10.1186/s13195-017-0320-4

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页数：10

共 100 条

[1] β-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase [J].