Brain Sugar Enzyme Trehalase Emerges as a Key Player in Aging and Neurodegeneration
Scientists discover trehalase is expressed in the human brain, where declining levels link to aging and multiple sclerosis via autophagy pathways.
Résumé
Researchers have identified for the first time that trehalase — an enzyme known for breaking down trehalose ('mushroom sugar') in the gut — is also expressed in the human brain. Analyzing post-mortem RNA sequencing data from two independent datasets, they found trehalase expression significantly decreases with age and in multiple sclerosis patients. Reduced trehalase correlated with shifts in gene networks governing autophagy, mitophagy, and neurodegeneration. Expression patterns also suggested cell-type specificity, with positive links to oligodendrocytes and a strong association with sirtuin 1 (SIRT1), a well-established neuroprotective protein. The findings position trehalose and its regulating enzyme as a potentially important axis in brain health and age-related neurological decline.
Résumé détaillé
Trehalose, a disaccharide sugar found abundantly in mushrooms and other organisms, has attracted scientific interest for its potential neuroprotective properties — particularly its ability to stimulate autophagy, the cellular 'self-cleaning' process that clears toxic protein aggregates linked to diseases like Alzheimer's and Parkinson's. However, whether the enzyme trehalase, which metabolizes trehalose, even exists in the human brain has remained an open question — until now.
Researchers from Tampere University analyzed two independent RNA-sequencing datasets derived from post-mortem human brain tissue to investigate trehalase gene expression and its potential role in neuroprotection. This approach allowed hypothesis testing across multiple brain regions and disease states without requiring live tissue, leveraging large existing biobank resources.
The study's headline finding is the first direct evidence that trehalase is expressed in the human brain. Beyond confirming its presence, the team found that trehalase expression significantly decreases in both aged donors and patients with multiple sclerosis compared to healthy controls. Differential gene correlation analysis revealed that trehalase-associated gene networks shift markedly with age, implicating pathways tied to autophagy, mitophagy, oxidative phosphorylation, and broader neurodegeneration cascades.
Cell-type analysis added further nuance: trehalase expression correlated positively with oligodendrocyte proportions across many brain regions but negatively with neuronal proportions in the hippocampus — a region critically affected in dementia. A robust positive association with sirtuin 1 (SIRT1) expression further anchors trehalase within known neuroprotective biology.
While these findings are observational and based on post-mortem data, they open a compelling new avenue of research. The authors propose trehalase as a candidate biomarker for neurodegeneration and suggest that the trehalase-trehalose axis may regulate cellular homeostasis in both neurons and glia. Future studies pairing trehalase gene expression with actual trehalose metabolite measurements in the same samples will be essential to validate these mechanisms.
Principales conclusions
- First direct evidence that trehalase enzyme is expressed in the human brain, not just the gut.
- Trehalase expression significantly decreases with age and in multiple sclerosis patients vs. controls.
- Age-related shifts in trehalase gene networks implicate autophagy, mitophagy, and neurodegeneration pathways.
- Trehalase expression positively correlates with oligodendrocyte proportions and strongly associates with SIRT1.
- Hippocampal trehalase expression shows inverse correlation with neuronal cell proportions.
Méthodologie
The study used RNA-sequencing data from two independent post-mortem human brain tissue datasets to analyze trehalase gene expression across age groups and disease conditions. Differential gene correlation analysis and pathway enrichment were applied to map trehalase-associated gene networks. Cell-type proportion estimates were used to assess cell-type specificity of expression patterns.
Limites de l'étude
All findings are based on post-mortem observational data, limiting causal inference. The study lacks paired trehalose metabolite measurements alongside gene expression, leaving the functional consequences of trehalase changes unconfirmed. Replication in larger cohorts and experimental validation in live models is needed.
Ce résumé vous a plu ?
Recevez les dernières recherches sur la longévité dans votre boîte de réception chaque semaine.
Saisissez votre e-mail pour vous abonner :