Is mental retardation a defect of synapse structure and function?

Mental retardation is believed to be a result of alterations in molecular pathways underlying neuronal processes involved in cognitive functions. It is not fully understood, however, which molecular pathways are critical for cognitive mechanisms. Furthermore, whether mental retardation is a developmental or ongoing disorder of cognitive functions is unknown. Answering these questions will help elucidate the etiology of mental retardation and possibly lead to new therapies. Several recently published studies suggested that mental retardation might be caused by defects in synapse structure and function. Four genes mutated in families with mental retardation encode proteins known as Rho guanine nucleotide exchange factor 6, oligophrenin-1, p21-activated kinase, and guanine dissociation inhibitor 1. Each of these interacts with various guanine nucleotide-binding proteins involved in signaling pathways that regulate the actin cytoskeleton, neurite outgrowth, neurotransmitter release, and dendritic spine morphology. The goal is to understand the roles of these genes in normal cognitive functions. (C) 2003 by Elsevier Inc. All rights reserved.