Journal
ANNUAL REVIEW OF NEUROSCIENCE, VOL 37
Volume 37, Issue -, Pages 17-38Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-neuro-071013-014100
Keywords
eIF2 alpha; mTOR; local protein synthesis; memory; autism; neurodegeneration
Categories
Funding
- NINDS NIH HHS [R01 NS076708] Funding Source: Medline
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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.
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