eIF2-dependent translation initiation: Memory consolidation and disruption in Alzheimer's disease

Memory storage is a conserved survivability feature, present in virtually any complex species. During the last few decades, much effort has been devoted to understanding how memories are formed and which molecular switches define whether a memory should be stored for a short or a long period of time. Among these, de novo protein synthesis is known to be required for the conversion of short-to long-term memory. There are a number translational control pathways involved in synaptic plasticity and memory consolidation, including the phos-phorylation of the eukaryotic initiation factor 2 alpha (eIF2 alpha), which has emerged as a critical molecular switch for long-term memory consolidation. In this review, we discuss findings pertaining to the requirement of de novo protein synthesis to memory formation, how local dendritic and axonal translation is regulated in neurons, and how these can influence memory consolidation. We also highlight the importance of eIF2 alpha-dependent translation initiation to synaptic plasticity and memory formation. Finally, we contextualize how aberrant phosphorylation of eIF2 alpha contributes to Alzheimer's disease (AD) pathology and how preventing disruption of eIF2-dependent translation may be a therapeutic avenue for preventing and/or restoring memory loss in AD.

Automated summary

This review discusses the requirement of de novo protein synthesis in memory formation and its mechanisms. It also introduces the regulation of local dendritic and axonal translation and its impact on memory consolidation. The review emphasizes the importance of eIF2α-dependent translation initiation in synaptic plasticity and memory formation, and explores the role of aberrant eIF2α phosphorylation in Alzheimer's disease.