重度抑郁症中自噬通路及其关键标志物的研究进展

doi:10.3969/j.issn.1674-8115.2023.10.015

上海交通大学学报（医学版） ›› 2023, Vol. 43 ›› Issue (10): 1324-1331.doi: 10.3969/j.issn.1674-8115.2023.10.015

• 综述 • 上一篇

重度抑郁症中自噬通路及其关键标志物的研究进展

李偲媛¹(), 和申¹, 李华芳¹^,²()

^1.上海交通大学医学院附属精神卫生中心精神科，上海 200030
^2.上海市精神心理疾病临床医学研究中心，上海市重性精神病重点实验室，上海 200030

收稿日期:2023-04-10 接受日期:2023-06-29 出版日期:2023-10-28 发布日期:2023-10-28
通讯作者: 李华芳 E-mail:lsy86781@163.com;lihuafang@smhc.org.cn
作者简介:李偲媛（1998—），女，住院医师，硕士生；电子信箱：lsy86781@163.com。
基金资助:
上海市精神心理疾病临床医学研究中心项目(19MC1911100);上海市精神卫生中心院级重点课题(2022zd02)

Recent advance in autophagy-related pathways and key biomarkers in major depressive disorder

LI Siyuan¹(), HE Shen¹, LI Huafang¹^,²()

^1.Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
^2.Shanghai Clinical Research Center for Mental Health, Shanghai Key Laboratory of Psychotic Disorders, Shanghai 200030, China

Received:2023-04-10 Accepted:2023-06-29 Online:2023-10-28 Published:2023-10-28
Contact: LI Huafang E-mail:lsy86781@163.com;lihuafang@smhc.org.cn
Supported by:
Project of Shanghai Clinical Research Center for Mental Health(19MC1911100);Shanghai Mental Health Center Fund(2022zd02)

摘要/Abstract

摘要：

重度抑郁症（major depressive disorder，MDD）是一种常见且严重的精神障碍，持续的心境低落是其主要的临床特征。MDD的病因复杂且具有高度异质性，目前尚未被完全阐明。抗抑郁药物是MDD主要的治疗方式之一，目前仍存在起效慢、治愈率低、安全性有待提高、患者依从性不足等问题，也一定程度上也反映了人们对MDD发病机制认识的不足。自噬（autophagy）是一种重要的维持稳态的细胞降解机制，与泛素?蛋白酶体系统一起维持细胞正常的新陈代谢。哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）是细胞自噬的重要调控因子。当细胞处于不良条件时，可以通过mTOR依赖性自噬通路或mTOR非依赖性自噬通路激活自噬。监测自噬水平的常用指标包括微管相关蛋白轻链3-Ⅱ （microtubule-associated protein light chain 3-Ⅱ，LC3-Ⅱ）、Bcl-2相互作用蛋白（Bcl-2 interacting coiled-coil protein 1，Beclin-1）和p62。近些年来，越来越多的研究提示，自噬信号通路异常可能参与了抑郁症的发展，抗抑郁治疗可能影响自噬，因此调控自噬信号通路可能是抑郁症有希望的治疗靶点。未来应加强中枢神经系统自噬信号通路的研究，为抑郁症与抗抑郁药物的机制研究提供更多可靠的证据。该文就mTOR依赖性自噬通路及mTOR非依赖性自噬通路与常见自噬标志物在抑郁症中的研究进展做一综述。

关键词: 重度抑郁症, 自噬, 自噬通路, 自噬标记物

Abstract:

Major depressive disorder (MDD) is a very common and severe mental disorder. Persistent emotional distress is one of its main clinical symptoms. The etiology of MDD is complex and highly heterogeneous, and has not yet been clarified. Antidepressant is a kind of important method for the treatment of MDD. However, there are still some problems such as slow onset of effect, low cure rate, safety to be further improved, and low compliance, which also reflect people's lack of understanding of the pathogenesis of MDD. Autophagy is a mechanism of cell degradation, which plays an important role in maintaining the stabilization of homeostasis. Mammalian target of rapamycin (mTOR) is an important regulator of autophagy, and adverse conditions can activate autophagy through mTOR-dependent or mTOR-independent autophagy pathways. Microtubule-associated protein light chain 3-Ⅱ (LC3-Ⅱ), Bcl-2 interacting coiled-coil protein 1 (Beclin-1) and p62 are common to be used in the measurement of autophagy flux. In recent years, more and more studies have shown that impaired autophagy may be involved in the development of MDD and antidepressant treatment may affect autophagy. Therefore, regulating impaired autophagy pathways may be a promising target of antidepressant treatment. In the future, more attention should be paid to the study of autophagy signaling pathway in the central nervous system to provide more reliable evidence for the mechanism of MDD and antidepressant treatment. This article introduces the roles of common mTOR-dependent autophagy pathways, mTOR-independent autophagy pathways and autophagic markers in the progression and treatment of MDD.

Key words: major depressive disorder (MDD), autophagy, autophagy-related pathway, autophagic biomarker

中图分类号:

R749

李偲媛, 和申, 李华芳. 重度抑郁症中自噬通路及其关键标志物的研究进展[J]. 上海交通大学学报（医学版）, 2023, 43(10): 1324-1331.

LI Siyuan, HE Shen, LI Huafang. Recent advance in autophagy-related pathways and key biomarkers in major depressive disorder[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(10): 1324-1331.

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重度抑郁症中自噬通路及其关键标志物的研究进展

Recent advance in autophagy-related pathways and key biomarkers in major depressive disorder

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