当前位置: X-MOL 学术Mol. Psychiatry › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Key role of Rho GTPases in motor disorders associated with neurodevelopmental pathologies
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2022-08-02 , DOI: 10.1038/s41380-022-01702-8
Evelyne Bloch-Gallego 1 , David I Anderson 2
Affiliation  

Growing evidence suggests that Rho GTPases and molecules involved in their signaling pathways play a major role in the development of the central nervous system (CNS). Whole exome sequencing (WES) and de novo examination of mutations, including SNP (Single Nucleotide Polymorphism) in genes coding for the molecules of their signaling cascade, has allowed the recent discovery of dominant autosomic mutations and duplication or deletion of candidates in the field of neurodevelopmental diseases (NDD). Epidemiological studies show that the co-occurrence of several of these neurological pathologies may indeed be the rule. The regulators of Rho GTPases have often been considered for cognitive diseases such as intellectual disability (ID) and autism. But, in a remarkable way, mild to severe motor symptoms are now reported in autism and other cognitive NDD. Although a more abundant litterature reports the involvement of Rho GTPases and signaling partners in cognitive development, molecular investigations on their roles in central nervous system (CNS) development or degenerative CNS pathologies also reveal their role in embryonic and perinatal motor wiring through axon guidance and later in synaptic plasticity. Thus, Rho family small GTPases have been revealed to play a key role in brain functions including learning and memory but their precise role in motor development and associated symptoms in NDD has been poorly scoped so far, despite increasing clinical data highlighting the links between cognition and motor development. Indeed, early impairements in fine or gross motor performance is often an associated feature of NDDs, which then impact social communication, cognition, emotion, and behavior. We review here recent insights derived from clinical developmental neurobiology in the field of Rho GTPases and NDD (autism spectrum related disorder (ASD), ID, schizophrenia, hypotonia, spastic paraplegia, bipolar disorder and dyslexia), with a specific focus on genetic alterations affecting Rho GTPases that are involved in motor circuit development.



中文翻译:

Rho GTPases 在与神经发育病理学相关的运动障碍中的关键作用

越来越多的证据表明,Rho GTP 酶和参与其信号通路的分子在中枢神经系统 (CNS) 的发育中起着重要作用。全外显子组测序 (WES) 和突变的从头检查,包括编码其信号级联分子的基因中的 S​​NP(单核苷酸多态性),使得最近发现显性常染色体突变以及候选基因的重复或缺失神经发育疾病(NDD)。流行病学研究表明,这些神经病理学中的几种同时发生可能确实是一种规律。Rho GTPases 的监管者经常被认为是认知疾病,如智力障碍 (ID) 和自闭症。但是,以一种不同寻常的方式,现在在自闭症和其他认知 NDD 中报告了轻微到严重的运动症状。尽管更丰富的文献报道了 Rho GTPases 和信号伙伴参与认知发展,但对它们在中枢神经系统 (CNS) 发育或退行性 CNS 病理学中的作用的分子研究也揭示了它们通过轴突引导和后来的胚胎和围产期运动布线中的作用在突触可塑性中。因此,已揭示 Rho 家族小 GTP 酶在包括学习和记忆在内的大脑功能中发挥关键作用,但迄今为止,尽管越来越多的临床数据强调了认知和记忆之间的联系,但它们在运动发育和 NDD 相关症状中的确切作用尚未确定。电机开发。事实上,精细或粗大运动表现的早期损伤通常是 NDD 的一个相关特征,它会影响社会交流、认知、情感和行为。

更新日期:2022-08-02
down
wechat
bug