Stress-Induced Dysregulation of Brain Iron Metabolism and Its Links to Neurological Disorders

Stress is a non-specific systemic response to internal or external challenges. Recent studies show that stress can disrupt iron metabolism and that iron dyshomeostasis is implicated in many diseases-particularly within the nervous system, where iron distribution and regulation intersect tightly with oxidative stress and inflammation. Activation of the hypothalamic-pituitary-adrenal (HPA) axis by stress can upregulate hepatic hepcidin and reprogram systemic iron fluxes, leading to functional iron deficiency and, in the brain, reduced iron availability, which affects myelination and neurotransmitter metabolism. Conversely, iron dyshomeostasis also contributes to neurodegenerative pathology. In this review, we synthesize recent evidence of how stress reprograms brain iron distribution and regulation, and we outline the mechanistic links between stress-induced iron dysregulation and neurological pathology. We also discuss the therapeutic implications (such as iron-chelation strategies) and highlight the three-way interplay among stress, iron metabolism, and neurodegeneration. These insights suggest that managing iron homeostasis may offer new therapeutic avenues for stress-related neural disorders.