The brain undergoes several changes at structural, molecular, and cellular levels leading to alteration in its functions and these processes are primarily maintained by proteostasis in cells. However, an imbalance in proteostasis due to the abnormal accumulation of protein aggregates induces endoplasmic reticulum (ER) stress. This event, in turn, activate the unfolded protein response; however, in most neurodegenerative conditions and brain injury, an uncontrolled unfolded protein response elicits memory dysfunction. Although the underlying signaling mechanism for impairment of memory function following induction of ER stress remains elusive, recent studies have highlighted that inactivation of a transcription factor, CREB, which is essential for synaptic function and memory formation, plays an essential role for ER stress-induced synaptic and memory dysfunction. In this review, current studies and most updated view on how ER stress affects memory function in both physiological and pathological conditions will be highlighted.

中文翻译：

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内质网应激，CREB和记忆：疾病中纠结的新兴环节。

大脑在结构，分子和细胞水平上经历数种变化，从而导致其功能发生改变，而这些过程主要由细胞中的蛋白稳态维持。但是，由于蛋白质聚集体的异常积聚而引起的蛋白稳态失衡会引起内质网（ER）应激。反过来，此事件会激活未折叠的蛋白质反应。但是，在大多数神经退行性疾病和脑损伤中，失控的未折叠蛋白反应会引发记忆功能障碍。尽管诱导内质网应激后记忆功能受损的潜在信号传导机制仍然难以捉摸，但最近的研究表明，转录因子CREB的失活对于突触功能和记忆形成至关重要，在内质网应激引起的突触和记忆功能障碍中起重要作用。在这篇综述中，将重点介绍有关内质网应激如何影响生理和病理状态下记忆功能的最新研究和最新观点。