# TPP-Thiazole Derivatives Ameliorate Psoriasiform Inflammation by Glycolysis Inhibition

## TL;DR

A new compound called MitoFu-O reduces psoriasis-like inflammation by targeting mitochondrial function and blocking harmful metabolic changes.

## Contribution

MitoFu-O is a novel mitochondria-targeting compound that ameliorates psoriasiform inflammation by inhibiting glycolysis and pro-inflammatory pathways.

## Key findings

- MitoFu-O reduces psoriasiform inflammation in mice and keratinocytes.
- MitoFu-O inhibits glycolytic enzymes and suppresses pro-inflammatory signaling pathways.
- Targeted mitochondrial modulation represents a promising therapeutic strategy for psoriasis.

## Abstract

Psoriasis, a chronic inflammatory skin disease, is driven by immune dysregulation and keratinocyte hyperproliferation, with current biologics facing limitations. Emerging evidence points to mitochondrial dysfunction and a pathological shift to aerobic glycolysis as core disease drivers. Here, we report that MitoFu-O, a novel mitochondria-targeting TPP-thiazole derivative, effectively ameliorates psoriasiform inflammation in imiquimod-induced mice and cytokine-stimulated keratinocytes. Mechanistically, MitoFu-O acts by inhibiting pathological glycolysis, downregulating key glycolytic enzymes (HK1, GAPDH, LDHA), and subsequently suppressing the activation of pivotal pro-inflammatory signaling pathways (MAPK, NF-κB, and STAT3). Our findings establish targeted mitochondrial modulation as a potent therapeutic strategy, positioning MitoFu-O as a promising lead compound that acts upstream of cytokine signaling by normalizing the metabolic reprogramming fundamental to psoriatic pathogenesis.