Exerkines mitigating Alzheimer's disease progression by regulating inflammation: Focusing on macrophage/microglial NLRP3 inflammasome pathway.

Recent research highlights the critical role of inflammation in accelerating amyloid beta and phosphorylated tubulin-associated protein tau cascade and Alzheimer's disease (AD) progression. Emerging evidence suggests that exercise influences AD by modulating inflammatory responses. We conducted a comprehensive search across multiple online databases. Our approach focused on previous and recent studies exploring the links among inflammation, AD, and the effects of exercise, specifically targeting research articles and books published in English. We pointed out that inflammation extends from the periphery to the central nervous system, facilitated by macrophage/microglial NLRP3 (nucleotide-binding domain, leucine rich-containing family, pyrin domain-containing protein 3) inflammasome signaling, which exacerbates classical AD mechanisms. Moreover, we provided further insights into the modulation of inflammasome signaling through exercise and exerkines, which may contribute to mitigating AD development. These insights deepen our understanding of AD mechanisms and offer the potential for identifying key therapeutic targets and biomarkers crucial for effective disease management and treatment. HIGHLIGHTS: Inflammation is potentially linked to the acceleration of classical Alzheimer's disease (AD) pathogenesis, including the pathways involving amyloid beta and phosphorylated tau, mediated by pro-inflammatory cytokines. Inflammation, initiated by the nucleotide-binding domain, leucine rich-containing family, pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathway within M1-type macrophages/microglia, may contribute to neuroinflammation and AD progression. Exercise has the potential to reduce inflammation and the development of AD by influencing NLRP3 inflammasome signaling via exerkines.