Exercise has been shown to beneficially impact Alzheimer's disease pathology by influencing amyloid precursor protein (APP) processing. The mechanisms involved are multifaceted and involve shifting APP processing away from the amyloidogenic pathway towards the non-amyloidogenic pathway. The production of Aβ peptides is regulated by the activity of β-secretase (BACE1), while the non-amyloidogenic pathway is regulated by α-secretase (ADAM10). Studies in animal and cell culture models have demonstrated that these exercise-induced alterations in APP processing lead to reduced Aβ production and improved cognitive performance. However, the mechanisms underlying these changes remain to be fully characterized. Emerging research points to exercise-induced factors as key elements in the regulation of APP processing.

The goal of this Research Topic is to provide a holistic overview of the potential mechanisms underlying the exercise-induced changes in amyloid precursor protein (APP) processing. By understanding how exercise can manipulate APP processing, the aim is to elucidate novel therapeutic targets and treatment strategies for Alzheimer’s disease. This Research Topic seeks to integrate findings from various researchers in exercise physiology and neuroscience fields, to offer a holistic understanding of the complex interplay between exercise, the brain, and APP processing.

To effectively address this topic, we welcome contributions that focus on and investigate:

- the molecular mechanisms of how exercise alters APP processing pathways, including α-, β-, and γ-secretase activities

- the role of exercise in modulating the content and activity of enzymes responsible for the clearance of Ab peptides

- exercise-induced signaling pathways that may influence APP processing and/or amyloid beta clearance or degradation

- novel therapeutic avenues and treatments emerging from the study of these interactions

We particularly welcome original research articles, holistic reviews, and perspective pieces. Authors should follow the journal's guidelines for manuscript preparation and submission, ensuring that their work meets the highest standards of scientific rigor and clarity.

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Frontiers in Cellular Neuroscience

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