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阐明异常细胞外调节激酶(ERK)信号与综合征性和非综合征性自闭症的关联。

Elucidation of Abnormal Extracellular Regulated Kinase (ERK) Signaling and Associations with Syndromic and Non-syndromic Autism.

机构信息

Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India.

出版信息

Curr Drug Targets. 2021;22(9):1071-1086. doi: 10.2174/1389450121666201020155010.

Abstract

Autism is a highly inherited and extremely complex disorder in which results from various cases indicate chromosome anomalies, unusual single-gene mutations, and multiplicative effects of particular gene variants, characterized primarily by impaired speech and social interaction and restricted behavior. The precise etiology of Autism Spectrum Disorder (ASD) is currently unclear. The extracellular signal-regulated kinase (ERK) signaling mechanism affects neurogenesis and neuronal plasticity during the development of the central nervous mechanism. In this regard, the pathway of ERK has recently gained significant interest in the pathogenesis of ASD. The mutation occurs in a few ERK components. Besides, the ERK pathway dysfunction lies in the upstream of modified translation and contributes to synapse pathology in syndromic types of autism. In this review, we highlight the ERK pathway as a target for neurodevelopmental disorder autism. In addition, we summarize the regulation of the ERK pathway with ERK inhibitors in neurological disorders. In conclusion, a better understanding of the ERK signaling pathway provides a range of therapeutic options for autism spectrum disorder.

摘要

自闭症是一种高度遗传性且极其复杂的疾病,各种研究结果表明该病与染色体异常、异常的单基因突变以及特定基因变异的倍增效应有关,其主要特征是言语和社交互动受损以及行为受限。自闭症谱系障碍(ASD)的确切病因目前尚不清楚。细胞外信号调节激酶(ERK)信号机制在中枢神经系统发育过程中影响神经发生和神经元可塑性。在这方面,ERK 通路最近在 ASD 的发病机制中引起了广泛关注。该通路中的几个 ERK 成分发生突变。此外,ERK 通路功能障碍位于已修改翻译的上游,导致自闭症综合征型的突触病理学。在这篇综述中,我们强调 ERK 通路是神经发育障碍自闭症的一个靶点。此外,我们总结了 ERK 抑制剂在神经疾病中的调节作用。总之,对 ERK 信号通路的更好理解为自闭症谱系障碍提供了一系列治疗选择。

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