title: Translational control in synaptic plasticity and cognitive dysfunction.
abstract: Activity-dependent changes in the strength of synaptic connections are fundamental to the formation and maintenance of memory. The mechanisms underlying persistent changes in synaptic strength in the hippocampus, specifically long-term potentiation and depression, depend on new protein synthesis. Such changes are thought to be orchestrated by engaging the signaling pathways that regulate mRNA translation in neurons. In this review, we discuss the key regulatory pathways that govern translational control in response to synaptic activity and the mRNA populations that are specifically targeted by these pathways. The critical contribution of regulatory control over new protein synthesis to proper cognitive function is underscored by human disorders associated with either silencing or mutation of genes encoding proteins that directly regulate translation. In light of these clinical implications, we also consider the therapeutic potential of targeting dysregulated translational control to treat cognitive disorders of synaptic dysfunction.
authors.affiliation: Department of Neuroscience, Memory and Brain Research Center, Baylor College of Medicine, Houston, Texas 77030; email: shelly.buffington@bcm.edu , wei.huang@bcm.edu , costamat@bcm.edu.
authors.forename: Shelly A
authors.initials: SA
authors.lastname: Buffington
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Mauro
authors.initials: M
authors.lastname: Costa-Mattioli
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000235:genetics* / Q000503:physiopathology*; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins
keywords: autism; eIF2α; local protein synthesis; mTOR; memory; neurodegeneration