Srinivasan Vignesh, Korhonen Laura, Lindholm Dan
Medicum, Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Minerva Foundation Institute for Medical Research, Biomedicum Helsinki 2U, Helsinki, Finland.
Front Cell Neurosci. 2020 Sep 29;14:554548. doi: 10.3389/fncel.2020.554548. eCollection 2020.
Neurons are polarized in structure with a cytoplasmic compartment extending into dendrites and a long axon that terminates at the synapse. The high level of compartmentalization imposes specific challenges for protein quality control in neurons making them vulnerable to disturbances that may lead to neurological dysfunctions including neuropsychiatric diseases. Synapse and dendrites undergo structural modulations regulated by neuronal activity involve key proteins requiring strict control of their turnover rates and degradation pathways. Recent advances in the study of the unfolded protein response (UPR) and autophagy processes have brought novel insights into the specific roles of these processes in neuronal physiology and synaptic signaling. In this review, we highlight recent data and concepts about UPR and autophagy in neuropsychiatric disorders and synaptic plasticity including a brief outline of possible therapeutic approaches to influence UPR and autophagy signaling in these diseases.
神经元在结构上是极化的，其细胞质区室延伸至树突，还有一条终止于突触的长轴突。高度的区室化给神经元中的蛋白质质量控制带来了特定挑战，使它们容易受到可能导致神经功能障碍（包括神经精神疾病）的干扰。突触和树突会经历由神经元活动调节的结构调制，这涉及关键蛋白质，这些蛋白质需要严格控制其周转率和降解途径。未折叠蛋白反应（UPR）和自噬过程研究的最新进展为这些过程在神经元生理学和突触信号传导中的特定作用带来了新的见解。在本综述中，我们重点介绍了关于神经精神疾病和突触可塑性中UPR和自噬的最新数据和概念，包括对影响这些疾病中UPR和自噬信号传导的可能治疗方法的简要概述。
