FNDC5 and Alzheimer disease: Liu et al. (2020) observed that short-term resistance training in a 3xTg AD mouse model increased irisin expression, reduced microglial activation in the hippocampus, and decreased levels of TNF-α and IL-1β mRNA. Concurrently, anti-inflammatory IL-10 expression increased. These effects indicate that FNDC5/irisin signaling, activated during exercise, enhances neuroinflammatory responses by modulating microglial activity and potentially inhibiting TNF-α-induced necroptosis (Kim et al., 2025).