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Progress of TRAF6 in the pathogenesis of depression: opportunities and challenges from molecular mechanisms to therapeutic targets.

Created on 20 Aug 2026

Authors

Xue-He Luo, Wei Guan

Published in

Biochemical pharmacology. Volume 243. Issue Pt 1. Pages 117461. Epub Oct 25, 2025.

Abstract

Depression is a common mental illness characterised by core symptoms such as low mood, diminished interest, and cognitive dysfunction. Its pathogenesis is complex, involving multiple factors, including neurotransmitter imbalances, immune-inflammatory disorders, and abnormal neuroplasticity. Recently, the role of neuroinflammatory mechanisms in the development of depression has garnered increasing attention. As a member of the tumour necrosis factor receptor-associated factor (TRAF) family, TRAF6 has attracted particular interest due to its significant role in immune and inflammatory responses. As a ubiquitin E3 ligase, TRAF6 exerts its physiological functions primarily through the Toll-like receptor 4 signalling pathway, activating subsequent transcriptional responses via the NF-κB and MAPK pathways. Moreover, an increasing number of studies have shown that TRAF6 is closely associated with central nervous system diseases, such as traumatic brain injury, Alzheimer's disease, and neuropathic pain. As a key regulator of immune-inflammatory signalling pathways, TRAF6 may contribute to the pathological processes of depression by mediating neuroinflammation and affecting neuroplasticity and neurogenesis. Therefore, this review summarises and analyses the current research on TRAF6 and its potential roles in depression. Our findings suggest that targeting TRAF6 offers a new strategy for treating depression.

PMID:
42619006
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

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