Translational control in the brain in health and disease

WS Sossin, M Costa-Mattioli - Cold Spring Harbor …, 2019 - cshperspectives.cshlp.org
Cold Spring Harbor perspectives in biology, 2019cshperspectives.cshlp.org
Translational control in neurons is crucially required for long-lasting changes in synaptic
function and memory storage. The importance of protein synthesis control to brain processes
is underscored by the large number of neurological disorders in which translation rates are
perturbed, such as autism and neurodegenerative disorders. Here we review the general
principles of neuronal translation, focusing on the particular relevance of several key
regulators of nervous system translation, including eukaryotic initiation factor 2α (eIF2α), the …
Translational control in neurons is crucially required for long-lasting changes in synaptic function and memory storage. The importance of protein synthesis control to brain processes is underscored by the large number of neurological disorders in which translation rates are perturbed, such as autism and neurodegenerative disorders. Here we review the general principles of neuronal translation, focusing on the particular relevance of several key regulators of nervous system translation, including eukaryotic initiation factor 2α (eIF2α), the mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1), and the eukaryotic elongation factor 2 (eEF2). These pathways regulate the overall rate of protein synthesis in neurons and have selective effects on the translation of specific messenger RNAs (mRNAs). The importance of these general and specific translational control mechanisms is considered in the normal functioning of the nervous system, particularly during synaptic plasticity underlying memory, and in the context of neurological disorders.
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