Page 37 - GPD-4-2

Gene & Protein in Disease

REVIEW ARTICLE
Orexin in depression: Evidence from basic and

clinical research

2
1
1
Chen Dong 1 , Yaping Sun , Jiawei Xu , Shuoshuo Guo , Ying Wang * ,
1
1,3
Shuangyu Lv * , and Xinying Ji *
1,4
1 Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical
Sciences, Henan University, Kaifeng, Henan, China
2 Department of Anesthesiology, The First Affiliated Hospital of Henan University, Henan University,
Kaifeng, Henan, China
3 Department of Neurosurgery, The First Affiliated Hospital of Henan University, Henan University,
Kaifeng, Henan, China
4 Center for Molecular Medicine, Faculty of Basic Medical Subjects, Shu-Qing Medical College of
Zhengzhou, Zhengzhou, Henan, China

Abstract

*Corresponding authors: Orexin – a neuropeptide – is extensively distributed in the central nervous system
Ying Wang and is involved in the regulation of diverse physiological functions and behaviors.
(wangy1528@126.com)
Shuangyu Lv Orexin is strongly associated with the onset and development of depression. The
(shuangyulv@henu.edu.cn) most important function of orexin is to interact with the transport system, mediating
Xinying Ji arousal, and energy homeostasis. Hypothalamic-ventral tegmental and hypothalamic-
(jixinying@zzsqmc.edu.cn)
ventral thalamic pathways provide clues for understanding the function of orexin and
Citation: Dong C, Sun Y, Xu J, et related disorders, such as sleep disorders, eating disorders, and substance abuse. This
al. Orexin in depression: Evidence
from basic and clinical research. article summarizes the basic and clinical studies on the role of the orexin system in
Gene Protein Dis. 2025;4(2):4210. regulating and treating depression, including the relationship between the expression
doi: 10.36922/gpd.4210 level of orexin in specific brain areas and diseases, relationship between adolescent
Received: July 11, 2024 depression and orexin, orexin receptor antagonists as a treatment for depression, and
narcolepsy, which is closely associated with depression. Research progress on the
1st revised: September 28, 2024
role of orexin in depression and recent relevant studies are summarized, providing
2nd revised: October 16, 2024 novel directions for developing depression treatment strategies.
3rd revised: October 27, 2024
4th revised: November 11, 2024 Keywords: Orexin; Depression; Sleep; Major depressive disorder; Neuron
Accepted: November 12, 2024
Published online: December 13,
2024 1. Introduction
Copyright: © 2024 Author(s).
This is an Open-Access article Orexin – or hypocretin – is a neuropeptide produced by neurons in the perifornical region,
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distributed under the terms of the lateral hypothalamus (LH), and dorsomedial hypothalamus, as well as by the proteolytic
Creative Commons Attribution cleavage of a precursor peptide. Orexin comprises two neuropeptides, orexin-A (OXA)
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License, permitting distribution,
and reproduction in any medium, and orexin-B (OXB), originating from a shared precursor released by neurons in the
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provided the original work is hypothalamus. The molecular structures of OXA and OXB comprise 33 and 28 amino
properly cited. acids, respectively (Figure 1). OXA and OXB are formed by cutting the same anterior
Publisher’s Note: AccScience orexin in neurons on the lateral and posterior hypothalamus and distributed throughout
Publishing remains neutral with the brain. There are two types of orexin receptors, namely, orexin receptor 1 (OX1R) and
regard to jurisdictional claims in
published maps and institutional orexin receptor 2 (OX2R). OXA exhibits equal affinity for both receptors, whereas OXB
affiliations. preferentially binds to OX2R. Orexin nerve fibers project to the spinal cord and wide

Volume 4 Issue 2 (2025) 1 doi: 10.36922/gpd.4210