Kim Pitna
Department of Cell, Developmental, and Integrative Biology (CDIB), University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Biomol Ther (Seoul). 2024 Mar 1;32(2):183-191. doi: 10.4062/biomolther.2023.181.
The Unfolded Protein Response (UPR) serves as a critical cellular mechanism dedicated to maintaining protein homeostasis, primarily within the endoplasmic reticulum (ER). This pathway diligently responds to a variety of intracellular indicators of ER stress with the objective of reinstating balance by diminishing the accumulation of unfolded proteins, amplifying the ER's folding capacity, and eliminating slow-folding proteins. Prolonged ER stress and UPR irregularities have been linked to a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. This review offers a comprehensive overview of the UPR pathway, delineating its activation mechanisms and its role in the pathophysiology of neuropsychiatric disorders. It highlights the intricate interplay within the UPR and its profound influence on brain function, synaptic perturbations, and neural developmental processes. Additionally, it explores evolving therapeutic strategies targeting the UPR within the context of these disorders, underscoring the necessity for precision and further research to effective treatments. The research findings presented in this work underscore the promising potential of UPR-focused therapeutic approaches to address the complex landscape of neuropsychiatric disorders, giving rise to optimism for improving outcomes for individuals facing these complex conditions.
未折叠蛋白反应（UPR）是一种关键的细胞机制，主要用于维持内质网（ER）内的蛋白质稳态。该途径会积极响应内质网应激的各种细胞内指标，旨在通过减少未折叠蛋白的积累、增强内质网的折叠能力以及清除折叠缓慢的蛋白来恢复平衡。内质网应激的长期存在和未折叠蛋白反应的异常与一系列神经精神疾病有关，包括重度抑郁症、双相情感障碍和精神分裂症。本综述全面概述了未折叠蛋白反应途径，阐述了其激活机制及其在神经精神疾病病理生理学中的作用。它强调了未折叠蛋白反应内部的复杂相互作用及其对脑功能、突触紊乱和神经发育过程的深远影响。此外，它还探讨了针对这些疾病中未折叠蛋白反应的不断发展的治疗策略，强调了精准性的必要性以及进一步研究有效治疗方法的重要性。这项工作中提出的研究结果强调了以未折叠蛋白反应为重点的治疗方法在应对神经精神疾病复杂局面方面的巨大潜力，为改善面临这些复杂病症的个体的治疗效果带来了乐观的前景。
