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 phosphorylation of the eukaryotic initiation factor 2 alpha (eIF2α), 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 eIF2α-dependent translation initiation to synaptic plasticity and memory formation. Finally, we contextualize how aberrant phosphorylation of eIF2α 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.

记忆存储是一种保守的生存能力特征，几乎存在于任何复杂物种中。在过去的几十年里，人们付出了大量的努力来了解记忆是如何形成的，以及哪些分子开关定义了记忆应该被短期存储还是长期存储。其中，已知蛋白质从头合成是短期记忆向长期记忆转变所必需的。突触可塑性和记忆巩固涉及许多翻译控制途径，包括真核起始因子 2 α (eIF2α) 的磷酸化，它已成为长期记忆巩固的关键分子开关。在这篇综述中，我们讨论了与记忆形成所需的蛋白质从头合成、神经元中局部树突和轴突翻译如何调节以及这些如何影响记忆巩固有关的发现。我们还强调了 eIF2α 依赖性翻译起始对突触可塑性和记忆形成的重要性。最后，我们阐述了 eIF2α 的异常磷酸化如何导致阿尔茨海默病 (AD) 病理学，以及如何防止 eIF2 依赖性翻译的破坏可能成为预防和/或恢复 AD 记忆丧失的治疗途径。