Long-term running exercise alleviates cognitive dysfunction in APP/PSEN1 transgenic mice via enhancing brain...

Area of Science:

• Neuroscience
• Cell Biology
• Gerontology

Background:

• Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) peptide aggregation in the brain.
• Current AD treatments are limited, but exercise shows promise for cognitive enhancement.
• The mechanisms by which exercise benefits AD patients are not fully understood.

Purpose of the Study:

• To investigate if long-term exercise reduces Aβ accumulation by activating lysosomal function in a mouse model of AD.
• To explore the molecular pathways involved in exercise-induced lysosomal activation and Aβ clearance.

Main Methods:

• APP/PSEN1 transgenic mice underwent a 5-month running exercise regimen.
• Cognitive function was assessed, and brain tissues were analyzed biochemically for Aβ levels, lysosomal function markers, and key protein expressions.
• Key proteins analyzed included transcription factor EB (TFEB) and lysosomal enzymes cathepsin D and L.

Main Results:

• Long-term exercise significantly improved cognitive function in AD mice.
• Exercise enhanced lysosomal function and promoted Aβ clearance in the brain.
• Exercise increased nuclear translocation of TFEB, boosting lysosome biogenesis gene transcription.
• Levels of cathepsin D and L were elevated, indicating increased Aβ degradation capacity.

Conclusions:

• Exercise mitigates cognitive dysfunction in Alzheimer's disease by enhancing lysosomal function.
• The study identifies TFEB and AMPK-mediated pathways as crucial in exercise-induced lysosomal activation.
• Exercise promotes Aβ degradation through activated lysosomes, offering a potential therapeutic strategy for AD.