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Therapeutic potential of exerkines in neurodegenerative and mental disorders: a narrative review.

PMID: 41940019 · DOI: 10.3389/fphys.2026.1793043 · Frontiers in physiology, 2026 · Suwol Yang, Hye-Won Sang, Seoyeon Kim, Eun-Jeong Cho, Youngju Choi, Dong Woo Kang, Young C Jang, Dong-Ho Park, Hyo-Bum K
📄 Abstract

Neurodegenerative and mental disorders impose significant global disease burdens and pose serious social and economic challenges. Physical exercise (PE) exerts beneficial effects on brain health, contributing to a reduction in the risk of Alzheimer's disease (AD), Parkinson's disease (PD), depression, anxiety, and post-traumatic stress disorder (PTSD). To understand these effects of PE, a variety of molecules released from various tissues in response to PE have been discovered, which are collectively called 'exerkines'. In particular, the skeletal muscle acts as an endocrine organ, secreting exerkines and is included in the category of myokines that facilitate direct or indirect crosstalk between the muscle and the brain. Although muscles actively interact with organs such as the liver, pancreas, and adipose tissue, the precise mechanisms of muscle-brain communication have yet to be fully elucidated. In the skeletal muscle, the types of exerkines secreted and their effects vary depending on the PE modality. Furthermore, these exerkines can cross the blood-brain barrier (BBB) to exert direct effects or act indirectly

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