# Roles and Mechanisms of TRIM Family Proteins in Inflammation in the Brain and Beyond

## TL;DR

This review explores how TRIM proteins regulate inflammation in the brain and other tissues, highlighting their potential as therapeutic targets.

## Contribution

The paper systematically compares TRIM proteins' roles in neuroinflammation and peripheral inflammation, identifying research gaps and therapeutic potential.

## Key findings

- TRIM proteins regulate inflammatory signaling in microglia and neurons, with distinct roles in brain cells.
- TRIM proteins show both pro- and anti-inflammatory effects, with some roles being contradictory or under-researched.
- The review identifies knowledge gaps and suggests TRIM proteins as potential therapeutic targets with systemic effects to consider.

## Abstract

Neurodegeneration is closely linked to neuroinflammation and is frequently accompanied by comorbidities with inflammatory features. Tripartite motif (TRIM) proteins are known to play an important role in innate immunity and inflammatory signaling in various tissues and organs of the body, including the central nervous system. Among the main cell types of the brain, TRIMs’ functions in microglia are largely associated with the regulation of intracellular inflammatory signaling, while in neurons they mainly relate to cell survival and oxidative stress. Data concerning TRIMs’ activity in astrocytes remain limited. Many TRIM proteins exert similar pro- or anti-inflammatory effects in neuroinflammation and in other inflammatory disorders in the body, although for some members their roles are reported to be opposite, contradictory, or insufficiently characterized, highlighting the need for further research. The aim of this review was to summarize published data on the common mechanisms of TRIMs’ actions as modulators of inflammation, and compare available reports in the context of neuroinflammation and peripheral inflammatory pathologies. We suggested that such an analysis may be valuable for guiding future research—both by identifying existing gaps in knowledge and by supporting the rational selection of specific TRIM proteins for investigation as therapeutic targets, with careful consideration of their systemic effects.