Key result
Exercise-induced FNDC5 improves cognition by inhibiting neuroinflammation and enhancing hippocampal neurogenesis and synaptic plasticity.
Why the study?
Research on the modulation of FNDC5 by exercise and its ability to improve hippocampal cognitive function lacks a systematic and comprehensive understanding.
This review highlights the potential of exercise-induced FNDC5/irisin as a therapeutic target and biomarker for preventing and improving cognitive impairment in neurodegenerative and metabolic diseases.
Supports FNDC5/irisin as target for cognitive impairment; leaves open clinical translation pending trials.
Cognitive dysfunction often occurs in Alzheimer's disease, Parkinson's disease, cerebrovascular disease, or other neurodegenerative diseases, and can significantly impact the life quality of patients and create serious social, psychological, and economic burdens for individuals and their families. Numerous studies have confirmed that exercise can slow the decline in cognitive function through multiple pathways, in which fibronectin type III domain-containing protein 5 (FNDC5) plays an important role. However, the current research on the modulation of FNDC5 by exercise and its ability to improve hippocampal cognitive function lacks a systematic and comprehensive understanding. Therefore, this review focuses on the latest research progress regarding the role of exercise-induced FNDC5 in cognitive function, systematically reviews the positive effects of FNDC5 on cognitive function impairment caused by various factors, and clarifies the specific mechanisms by which exercise-induced FNDC5 improves cognitive function by inhibiting neuroinflammation and improving hippocampal neurogenesis and hippocampal synaptic plasticity. Based on the existing literature, we also identify the areas that require further research in this field. Overall, this review provides a theoretical basis for exercise-based prevention and improvement of cognitive function impairment.
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Zhao et al. (2025) conducted a review in Cognitive dysfunction. Exercise-induced FNDC5 was evaluated. Exercise-induced FNDC5 improves cognitive function by inhibiting neuroinflammation and enhancing hippocampal neurogenesis and synaptic plasticity.
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