AUTHOR=Saggu Shalini , Pless Andrew , Dew Emily , Ware Destany , Jiao Kai , Wang Qin 

TITLE=Monoamine signaling and neuroinflammation: mechanistic connections and implications for neuropsychiatric disorders

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1543730

DOI=10.3389/fimmu.2025.1543730

ISSN=1664-3224

ABSTRACT=Monoamines, including norepinephrine, serotonin, and dopamine, orchestrate a broad spectrum of neurophysiological and homeostatic events. Recent research shows a pivotal role for monoaminergic signaling in modulating neuroinflammation by regulating proinflammatory cytokines and chemokines within the central nervous system. Importantly, this modulation is not unidirectional; released proinflammatory cytokines markedly “feedback” to influence the metabolism of monoamine neurotransmitters, impacting their synthesis, release, and reuptake. This bidirectional interplay significantly links monoaminergic pathways and neuroinflammatory responses. In this review, we summarize current knowledge of the dynamic interactions between monoamine signaling and neuroinflammation, as well as their critical implications for the pathophysiology of neuropsychiatric disorders, including Parkinson’s Disease, Major Depressive Disorder, and Alzheimer’s Disease. By integrating recent findings, we shed light on potential therapeutic targets within these interconnected pathways, providing insights into novel treatment strategies for these devastating disorders.