# TFEB, FOXO3 and TLR4 in resveratrol-induced autophagy in a mucopolysaccharidosis IIIB mouse model

## TL;DR

Resveratrol improves brain function and reduces inflammation in a mouse model of a rare genetic disorder called mucopolysaccharidosis IIIB.

## Contribution

The study identifies FOXO3 as a key factor in resveratrol-induced autophagy in MPS IIIB mice.

## Key findings

- Resveratrol reduces sugar accumulation and improves behavior in MPS IIIB mice.
- Resveratrol decreases inflammation in the brain and body of affected mice.
- Autophagy and immune response are disturbed in MPS IIIB mice.

## Abstract

Mucopolysaccharidosis (MPS) type IIIB is the progressive degeneration of the central nervous system. Resveratrol is proposed as a potential therapeutic molecule as a drug reducing inflammation and for improving behavior of MPS mice. Here we investigated autophagy in correlation with immune response in an MPS IIIB mouse model. The effects of resveratrol on mouse behavior and the levels of selected cytokines that influence the inflammation were assessed. The study was performed on both male and female mice treated or not with resveratrol. The results of behavioral, molecular and biochemical experiments confirmed that autophagy and immune response are disturbed in MPS IIIB mice. A correlation between behavioral disturbances and levels of heparan sulfate and TLR4 could be observed. The FOXO3 transcription factor was identified as one of the key factors in the resveratrol-mediated stimulation of the autophagy process in the MPS IIIB mouse model, though it was not the sole pathway induced by this compound. We conclude that resveratrol can modulate the degradation of glycosaminoglycans and also may contribute to the reduction of inflammation and the normalization of animal behavior in the MPS IIIB model.

Mucopolysaccharidosis (MPS) is a rare genetic disorder that affects the body’s ability to break down certain sugars. Sanfilippo disease, or MPS III, is particularly damaging to the brain. Here researchers explored the potential of resveratrol, a natural compound with anti-inflammatory properties, as a treatment. The study used a mouse model of MPS IIIB to test resveratrol’s effects. Mice were given resveratrol from 8 weeks old and monitored until 30 weeks. The researchers measured sugar levels in urine and conducted behavioral tests to assess improvements. They also examined how resveratrol affected inflammation and brain function. The results showed that resveratrol reduced sugar accumulation and improved behavior in both male and female mice. It also decreased inflammation in the brain and body. The study concluded that resveratrol could be a promising treatment for MPS III by enhancing autophagy and reducing inflammation.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.