This is a multigenic model again, even though the primary genetic effect may have a single major effect locus. Thus, with regard to the molecular mechanism of global regulation of gene expression, multiple studies demonstrate that selleck Vandetanib neurodevelopmental processes are sensitive to the dosage of a wide variety of genes, likely contributing to autism. Such processes most likely include experience-dependent modulation of neural networks via synaptogenesis and synaptic plasticity because such events appear to rely on a large and dynamic array of genes rather than some other genetically preprogrammed response that may be more confined in Inhibitors,research,lifescience,medical gene usage and thereby show more

Mendelian inheritance. This also may explain why more overt signs of autism do not manifest until a later “critical period” of cognitive development and perhaps why there is a period Inhibitors,research,lifescience,medical of normal development in RTT patients followed by a regression in development. Such a regression

may reflect an inability of neurons and neuronal circuits to properly adapt to environmental stimuli. Protein localization, translation, and turnover The synapse plays host to a number of critical events for proper Inhibitors,research,lifescience,medical neuronal function including neurotransmitter release, synaptic vesicle recycling, and postsynaptic receptor activation and recycling. Inhibitors,research,lifescience,medical Such a dynamic environment poses a challenge for the cellular selleck chemical Bosutinib machinery responsible for protein synthesis and degradation because numerous molecules must work together in a precise manner to mediate these

events and produce downstream effects like activity-dependent synaptic plasticity. Thus, it is conceivable that disruptions of any single one of these components could have a deleterious effect at the Inhibitors,research,lifescience,medical synapse. Alternatively, we can imagine a molecular mechanism whereby multiple features of the synaptic machinery are altered via the perturbation of an upstream regulator of these features, such as local protein Anacetrapib regulation. Current genetic data seems to suggest both mechanisms contribute to the pathogenesis, however, they converge on neurodevelopmental processes dependent on the synapse. For example, mutations contributing to syndromic forms of autism have been discovered in fragile X mental retardation 1 (FMR1) and cytoplasmic FMR1-interacting protein 1 (CYFIP1), which are genes encoding for negative translational regulators.50 Loss of function of such genes consequently enhances local protein translation altering synaptic plasticity. In fact, local translational regulation was first revealed as a central mechanism in proper neurodevelopment by studies of FXS, a disorder caused by hypermethylation of FMR1 and subsequent loss of fragile X mental retardation protein (FMRP) expression.