Sect. Behavioural Neuroscience, Department of Cell Biology & Neuroscience, Istituto Superiore di Sanità, Roma, Italy.
Sect. Behavioural Neuroscience, Department of Cell Biology & Neuroscience, Istituto Superiore di Sanità, Roma, Italy; Bambino Gesù, Children Hospital, IRCCS, Roma, Italy.
Neurosci Biobehav Rev. 2014 Oct;46 Pt 2:285-301. doi: 10.1016/j.neubiorev.2014.06.007. Epub 2014 Jun 24.
Rho GTPases are key intracellular signaling molecules that coordinate dynamic changes in the actin cytoskeleton, thereby stimulating a variety of processes, including morphogenesis, migration, neuronal development, cell division and adhesion. Deviations from normal Rho GTPases activation state have been proposed to disrupt cognition and synaptic plasticity. This review focuses on the functional consequences of genetic ablation of upstream and downstream Rho GTPases molecules on cognitive function and neuronal morphology and connectivity. Available information on this issue is described and compared to that gained from mice carrying mutations in the most studied Rho GTPases and from pharmacological in vivo studies in which brain Rho GTPases signaling was modulated. Results from reviewed literature provide definitive evidence of a compelling link between Rho GTPases signaling and cognitive function, thus supporting the notion that Rho GTPases and their downstream effectors may represent important therapeutic targets for disorders associated with cognitive dysfunction.
Rho GTPases 是细胞内信号分子的关键，协调肌动蛋白细胞骨架的动态变化，从而刺激多种过程，包括形态发生、迁移、神经元发育、细胞分裂和黏附。从正常的 Rho GTPases 激活状态的偏差被提出破坏认知和突触可塑性。这篇综述重点介绍了上游和下游 Rho GTPases 分子的遗传缺失对认知功能和神经元形态和连接的功能后果。描述了关于这个问题的现有信息，并与最受研究的 Rho GTPases 突变的小鼠以及在体内药理学研究中调节大脑 Rho GTPases 信号的信息进行了比较。综述文献的结果提供了 Rho GTPases 信号与认知功能之间存在紧密联系的明确证据，从而支持 Rho GTPases 及其下游效应物可能是与认知功能障碍相关的疾病的重要治疗靶点的观点。
