Language

English

Publication Date

10-29-2025

Journal

Molecular Neurodegeneration

DOI

10.1186/s13024-025-00905-1

PMID

41163155

PMCID

PMC12570858

PubMedCentral® Posted Date

10-29-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Microglia are the resident immune cell of the brain, and alterations in microglia signaling have been implicated in many neurodegenerative disorders. While microglia responses to central cues and other brain cell types are well documented, studies are increasingly investigating the impact of peripherally derived signals on microglia function. A diverse array of peripheral cues, including dietary components, hormones, and bacteria metabolites and components from the microbiome cross the blood brain barrier and directly influence microglia state through ligand-receptor interactions. This review highlights the complexity of brain-body interactions from the perspective of microglia function and proposes the idea that microglia could serve as a central hub of detection and regulation of body state changes. In addition, improving understanding of how microglia respond to peripheral cues will allow for improved preclinical experimental design. As peripheral cues have the potential to be more readily manipulated than central cues, these interactions also have implications for the treatment of many diseases and neurodegenerative disorders.

Keywords

Humans, Microglia, Animals, Brain, Signal Transduction, Neurodegenerative Diseases, Blood-Brain Barrier, Microglia, Central nervous system, Peripheral cues, Neurodegenerative disease, Neurons

Published Open-Access

yes

13024_2025_905_Figa_HTML.jpg (57 kB)
Graphical Abstract

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