Vithayathil Joseph, Pucilowska Joanna, Landreth Gary E
Department of Neurosciences, Case Western Reserve University, Cleveland, OH, United States.
Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States.
Prog Brain Res. 2018;241:63-112. doi: 10.1016/bs.pbr.2018.09.008. Epub 2018 Nov 1.
The MAPK pathway is a prominent intracellular signaling pathway regulating various intracellular functions. Components of this pathway are mutated in a related collection of congenital syndromes collectively referred to as neuro-cardio-facio-cutaneous syndromes (NCFC) or Rasopathies. Recently, it has been appreciated that these disorders are associated with autism spectrum disorders (ASD). In addition, idiopathic ASD has also implicated the MAPK signaling cascade as a common pathway that is affected by many of the genetic variants that have been found to be linked to ASDs. This chapter describes the components of the MAPK pathway and how it is regulated. Furthermore, this chapter will highlight the various functions of the MAPK pathway during both embryonic development of the central nervous system (CNS) and its roles in neuronal physiology and ultimately, behavior. Finally, we will summarize the perturbations to MAPK signaling in various models of autism spectrum disorders and Rasopathies to highlight how dysregulation of this pivotal pathway may contribute to the pathogenesis of autism.
丝裂原活化蛋白激酶(MAPK)信号通路是一种重要的细胞内信号通路,可调节多种细胞内功能。该信号通路的组成部分在一系列相关的先天性综合征中发生突变,这些综合征统称为神经-心脏-面部-皮肤综合征(NCFC)或Ras相关疾病。最近,人们认识到这些疾病与自闭症谱系障碍(ASD)有关。此外,特发性ASD也表明MAPK信号级联是一条常见途径,许多已发现与ASD相关的基因变异都会影响该途径。本章描述了MAPK信号通路的组成部分及其调节方式。此外,本章将重点介绍MAPK信号通路在中枢神经系统(CNS)胚胎发育过程中的各种功能,以及它在神经元生理学乃至行为中的作用。最后,我们将总结自闭症谱系障碍和Ras相关疾病的各种模型中MAPK信号的扰动情况,以突出这条关键信号通路的失调如何可能导致自闭症的发病机制。