Serotonin (5-Hydroxytryptamine): Metabolism, Signaling, Biological Functions, Diseases, and Emerging Therapeutic Opportunities.
Level 5 - mechanism / opinion, no new human data
Narrative review of mechanistic literature and preclinical concepts without systematic review methodology.
PubMed 40937192 · doi:10.1002/mco2.70383
What was done
This narrative review synthesized current literature on serotonin (5-HT) metabolism (biosynthesis, transport, and degradation), 5-HT receptor pathways (spanning seven receptor families and 14 subtypes), and its biological roles across physiological systems, disease states, and the tumor immune microenvironment.
What was found
The abstract presents a qualitative overview without reporting quantitative data, effect sizes, or study counts. It notes that 5-HT dysregulation is implicated in gastrointestinal disorders, psychiatric illnesses, metabolic disorders, and cancer. It specifically outlines mechanistic effects on tumor immunity—including macrophage polarization, dendritic cell function, T cell activity, and PD-L1 expression—and highlights proposed therapeutic strategies such as combining selective serotonin reuptake inhibitors (SSRIs) with immune checkpoint inhibitors, inhibiting metabolic enzymes (e.g., Tph1, MAO-A), and using receptor-specific agents such as 5-HT7 receptor antagonists.
Why it matters
The review frames the peripheral and central serotonin systems, particularly their immune-modulating aspects, as emerging targets for multimodal therapy in oncology and metabolic disease.
Limits
As a broad narrative review, the paper does not use systematic search or meta-analytic methods, and the abstract provides no primary human clinical data or quantitative metrics. Many of the highlighted immunological and oncological targets remain at the preclinical or theoretical stage.
Cited by
- supports There are 14 distinct serotonin receptor subtypes.