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Prog Brain Res. 2018;241:63-112. doi: 10.1016/bs.pbr.2018.09.008. Epub 2018 Nov 1.

ERK/MAPK signaling and autism spectrum disorders.

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Department of Neurosciences, Case Western Reserve University, Cleveland, OH, United States.
Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States. Electronic address:


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.


Autism spectrum disorders; Corticogenesis; ERK; MAP kinase; Neural progenitors; Rasopathies

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