Exercise-induced modulation of miRNAs and gut microbiome: a holistic approach to neuroprotection in Alzheimer’s disease

Abstract Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is marked by cognitive decline, neuroinflammation, and neuronal loss. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression, influencing key pathways involved in neuroinflammation and neurodegeneration in AD. This review delves into the multifaceted role of exercise in modulating miRNA expression and its interplay with the gut microbiome, proposing a comprehensive framework for neuroprotection in AD. By synthesizing current research, we elucidate how exercise-induced changes in miRNA profiles can mitigate inflammatory responses, promote neurogenesis, and reduce amyloid-beta and tau pathologies. Additionally, we explore the gut–brain axis, highlighting how exercise-driven alterations in gut microbiota composition can further influence miRNA expression, thereby enhancing cognitive function and reducing neuroinflammatory markers. This holistic approach underscores the potential of targeting exercise-regulated miRNAs and gut microbiome interactions as a novel, noninvasive therapeutic strategy to decelerate AD progression and improve quality of life for patients. This approach aims to decelerate disease progression and improve patient outcomes, offering a promising avenue for enhancing the effectiveness of AD management.