Trehalose restores functional autophagy suppressed by high glucose

Area of Science:

• Cell Biology
• Neuroscience
• Biochemistry

Background:

• Autophagy is crucial for neurulation.
• Trehalose, a natural disaccharide, is a potential autophagy activator with low toxicity.
• Understanding trehalose's direct role in autophagy is key for therapeutic applications.

Purpose of the Study:

• To investigate if trehalose directly induces autophagy.
• To elucidate the mechanism by which trehalose affects autophagosome formation and function.
• To assess trehalose's efficacy in reversing autophagy suppression caused by high glucose and maternal diabetes.

Main Methods:

• FITC-labeled trehalose was used to trace its presence in autophagosomes.
• Autophagosome formation and flux were measured in GFP-LC3 reporter cells and neural stem cells.
• Effects on p62 protein expression and autophagosome integrity were analyzed under high glucose conditions and in vivo models of maternal diabetes.

Main Results:

• Trehalose potently induced de novo autophagosome formation and increased autophagosome flux, comparable to rapamycin and starvation.
• Trehalose reversed high glucose-induced autophagy suppression and reduced p62 levels.
• Trehalose-induced autophagosomes were functionally active, mediating mitophagy and reticulophagy to clear damaged organelles in neuroepithelial cells affected by maternal diabetes.

Conclusions:

• Trehalose directly incorporates into and promotes the generation of functional autophagosomes.
• This direct action provides a mechanistic basis for trehalose's therapeutic potential in preventing autophagy-associated pathogenesis.
• Trehalose demonstrates significant promise in counteracting disruptions in autophagy caused by metabolic challenges like high glucose and maternal diabetes.