Marko Daniel M, Finch Michael S, Mohammad Ahmad, MacNeil Adam J, Klentrou Panagiota, MacPherson Rebecca E K
Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada.
Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada.
Am J Physiol Cell Physiol. 2022 Apr 1;322(4):C614-C623. doi: 10.1152/ajpcell.00418.2021. Epub 2022 Feb 23.
Neurodegenerative diseases such as Alzheimer's disease (AD) are becoming more prevalent in our aging society. One specific neuropathological hallmark of this disease is the accumulation of amyloid-β (Aβ) peptides, which aggregate to form extraneuronal plaques. Increased Aβ peptides are often observed well before symptoms of AD develop, highlighting the importance of targeting Aβ-producing pathways early on in disease progression. Evidence indicates that exercise has the capacity to reduce Aβ peptide production in the brain; however, the mechanisms remain unknown. Exercise-induced signaling mediators could be the driving force behind some of the beneficial effects observed in the brain with exercise. The purpose of this study was to examine if postexercise serum and the factors it contains can alter neuronal amyloid precursor protein (APP) processing. Human SH-SY5Y neuronal cells were differentiated with retinoic acid for 5 days and treated with 10% pre- or postexercise serum from humans for 30 min. Cells were collected for analysis of acute (30 min; = 6) or adaptive (24 h posttreatment; = 6) responses. There were no statistical differences in a disintegrin and metalloproteinase 10 (ADAM10) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) mRNA or protein expression with postexercise serum treatment at either time point. However, there was an increase in the ratio of soluble amyloid precursor protein α (sAPPα) to soluble amyloid precursor protein β (sAPPβ) protein content ( = 0.05) after 30 min of postexercise serum treatment. In addition, 30 min of postexercise serum treatment increased ADAM10 ( = 0.01) and BACE1 ( = 0.02) activity. These findings suggest that postexercise serum modulates important enzymes involved in APP processing, potentially pushing the cascade toward the nonamyloidogenic arm.
在我们这个老龄化社会中，诸如阿尔茨海默病（AD）之类的神经退行性疾病正变得越来越普遍。这种疾病的一个特定神经病理学特征是淀粉样β（Aβ）肽的积累，这些肽聚集形成细胞外斑块。在AD症状出现之前，通常就能观察到Aβ肽增加，这凸显了在疾病进展早期针对Aβ产生途径的重要性。有证据表明，运动有能力减少大脑中Aβ肽的产生；然而，其机制仍然未知。运动诱导的信号介质可能是运动在大脑中观察到的一些有益作用背后的驱动力。本研究的目的是检验运动后血清及其所含因子是否能改变神经元淀粉样前体蛋白（APP）的加工过程。人SH-SY5Y神经元细胞用视黄酸分化5天，并用来自人类的10%运动前或运动后血清处理30分钟。收集细胞用于分析急性（30分钟；n = 6）或适应性（处理后24小时；n = 6）反应。在两个时间点，运动后血清处理后，解整合素和金属蛋白酶10（ADAM10）以及β位点淀粉样前体蛋白裂解酶1（BACE1）的mRNA或蛋白表达均无统计学差异。然而，运动后血清处理30分钟后，可溶性淀粉样前体蛋白α（sAPPα）与可溶性淀粉样前体蛋白β（sAPPβ）的蛋白含量比值增加（P = 0.05）。此外，运动后血清处理30分钟增加了ADAM10（P = 0.01）和BACE1（P = 0.02）的活性。这些发现表明，运动后血清调节参与APP加工的重要酶，可能促使级联反应朝着非淀粉样生成途径发展。
