Work

The vicious cycle of neuroinflammation and ferroptosis in depression: mechanisms and therapeutic targets

Year: 2026

Type: article

Abstract: Depression is one of the leading causes of disability worldwide, yet its underlying mechanisms remain elusive. Both neuroinflammation and ferroptosis are known contributors to the disease, and understanding their interplay is critical for unraveling the pathogenesis of depression. This review explores the relationship between neuroinflammation and ferroptosis in the context of depression. We first delineate the core mechanisms of each process. Subsequently, we focus on the key signaling pathways bridging these processes, including cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING), nuclear factor kappa-B (NF-κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and nuclear factor erythroid 2-related factor 2 (Nrf2), and elucidate how this inflammation-ferroptosis vicious cycle contributes to depression. Finally, we highlight therapeutic agents targeting both processes, suggesting novel treatment directions. By showing that inflammation and ferroptosis form a vicious cycle, this work offers a clearer perspective on the pathogenesis of depression and identifies specific therapeutic targets for breaking this pathological loop.

Source: Frontiers in Neuroscience

DOI: 10.3389/fnins.2026.1819436

Authors: Leyi Yao, Ruyu Yan, Chong Sun

Institutions: Nanchang University, Second Affiliated Hospital of Nanchang University

Language: English

Topic: Tryptophan and brain disorders

Subfield: Biological Psychiatry

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801