APP Processing: A Biochemical Competition Influenced by Exercise-Induced Signalling Mediators

Abstract

In our aging society neurodegenerative diseases such as Alzheimer’s disease (AD) are becoming more prevalent. One specific neuropathological hallmark of this disease is excessive accumulation of amyloid-β (Aβ) peptides, which can aggregate to form the plaques commonly associated with this disease. These plaques are often observed well before symptoms of AD develop. Therefore, it is important to find ways to regulate the pathways involved in the production of these peptides. Evidence indicates that exercise has the capacity to reduce Aβ peptide production in the brain. Exercise promotes the release of many different signalling mediators from various tissues and organs in the body. These exercise-induced signalling mediators could be the driving force behind some of the beneficial effects seen in the brain with exercise. The purpose of this study was to examine if post-exercise serum and the factors it contains can alter neuronal APP processing. Human SH-SY5Y neuronal cells were differentiated with retinoic acid for 5 days and treated with 10% pre- or post-exercise serum for 30 minutes. Cells were collected for analysis of acute (30 minutes; n=6) or adaptive (24 hours post-treatment; n=6) responses. There were no statistical differences in ADAM10 and BACE1 mRNA or protein expression with post-exercise serum treatment at either time point. However, there was an increase in the ratio of sAPPα to sAPPβ protein content (p=0.05) after 30 minutes of post-exercise serum treatment. Additionally, 30 minutes of post-exercise serum treatment increased ADAM10 (p=0.01) and BACE1 (p=0.02) activity. These novel findings suggest that post-exercise serum modulates important enzymes involved in APP processing, potentially pushing the cascade towards the non-amyloidogenic arm.