| dc.description.abstract | Autism is unequivocally a complex genetic disorder. However, its complexity converges into the activity-dependent synapse plasticity. Compelling evidence suggests that the local dendritic protein synthesis constitutes a critical molecular mechanism underlying synapse plasticity. In this regard, the extracellular signal-regulated kinase (ERK) pathway has recently attracted considerable attention in ASD pathogenesis. At synapses, ERK regulates the recruitment of components of local translation machinery and thus stimulates protein synthesis in response to activity. Mutations in multiple ERK components occur in autism and disrupt ERK signaling. In vivo, these mutations disturb synapse function and cognition. Dysfunction of the ERK pathway additionally lies upstream of altered translation and contributes to synapse pathology in syndromic forms of autism. Collectively, these findings suggest that activity-dependent and ERK-mediated local protein synthesis may be an important component of the molecular basis of ASD. | |
