AUTHOR=Bedada Fikru B. , Ntekim Oyonumo E. , Nwulia Evaristus O. , Fungwe Thomas V. , Nadarajah Sheeba Raaj , Obisesan Thomas O. 

TITLE=Exercise Training-Increased FBXO32 and FOXO1 in a Gender-Dependent Manner in Mild Cognitively Impaired African Americans: GEMS-1 Study

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.641758

DOI=10.3389/fnagi.2021.641758

ISSN=1663-4365

ABSTRACT=<p>The ubiquitin proteasome system (UPS) and <italic>FOXOs</italic> transcription factors play a pivotal role in cellular clearance and minimizing the accumulation of Aβ in neurodegeneration (ND). In African Americans (AAs) with mild cognitive impairment (MCI), the role of components of UPS and <italic>FOXOs</italic>; and whether they are amenable to exercise effects is unknown. We hypothesized that exercise can enhance cellular clearance systems during aging and ND by increasing expressions of <italic>FBXO32</italic> and <italic>FOXO1</italic>. To test this hypothesis, we used TaqMan gene expression analysis in peripheral blood (PB) to investigate the component of UPS and <italic>FOXOs</italic>; and provide mechanistic insight at baseline, during exercise, and in both genders. At baseline, levels of <italic>FBXO32</italic> were higher in women than in men. In our attempt to discern gender-specific exercise-related changes, we observed that levels of <italic>FBXO32</italic> increased in men but not in women. Similarly, levels of <italic>FOXO1</italic> increased in men only. These data suggest that a graded dose of <italic>FBXO32</italic> and<italic> FOXO1</italic> may be beneficial when PB cells carrying <italic>FBXO32</italic> and<italic> FOXO1</italic> summon into the brain in response to Alzheimer’s disease (AD) perturbation (docking station PB cells). Our observation is consistent with emerging studies that exercise allows the trafficking of blood factors. Given the significance of <italic>FBXO32</italic> and <italic>FOXO1</italic> to ND and associated muscle integrity, our findings may explain, at least in part, the benefits of exercise on memory, associated gait, and balance perturbation acknowledged to herald the emergence of MCI.</p>