Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (6): 1210-1227.doi: 10.4103/1673-5374.325012

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All roads lead to Rome — a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer’s disease

Yi-Yao Liang1, 2, #, Li-Dan Zhang1, 2, #, Xi Luo1, 2, Li-Li Wu3, 4, Zhao-Wei Chen5, Guang-Hao Wei5, Kai-Qing Zhang5, Ze-An Du6, Ren-Zhi Li7, Kwok-Fai So1, 2, 8, 9, *, Ang Li1, 2, 8, *   

  1. 1Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong Province, China; 2Key Laboratory of CNS Regeneration (Jinan University), Ministry of Education, Guangzhou, Guangdong Province, China; 3Department of Medical Ultrasonics, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China; 4Guangdong Key Laboratory of Liver Disease Research, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 5Department of Clinical Medicine, School of Medicine, Jinan University, Guangzhou, Guangdong Province, China; 6Department of Clinical Medicine, International School, Jinan University, Guangzhou, Guangdong Province, China; 7International Department of the Affiliated High School of South China Normal University, Guangzhou, Guangdong Province, China; 8Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong Province, China; 9Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Online:2022-06-15 Published:2021-12-16
  • Contact: Kwok-Fai So, PhD, hrmaskf@hku.hk; Ang Li, MD, PhD, anglijnu@jnu.edu.cn.
  • Supported by:
    The work was supported by the National Natural Science Foundation of China, No. 82071372 (to AL); the Natural Science Foundation of Guangdong Province of China, No. 2021A1515011231 (to AL); Outstanding Scholar Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) of China, No. 2018GZR110102002 (to KFS and AL); and Science and Technology Program of Guangzhou of China, No. 202007030012 (to KFS and AL).

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Abstract: Age-related neurodegenerative disorders such as Alzheimer’s disease (AD) have become a critical public health issue due to the significantly extended human lifespan, leading to considerable economic and social burdens. Traditional therapies for AD such as medicine and surgery remain ineffective, impractical, and expensive. Many studies have shown that a variety of bioactive substances released by physical exercise (called “exerkines”) help to maintain and improve the normal functions of the brain in terms of cognition, emotion, and psychomotor coordination. Increasing evidence suggests that exerkines may exert beneficial effects in AD as well. This review summarizes the neuroprotective effects of exerkines in AD, focusing on the underlying molecular mechanism and the dynamic expression of exerkines after physical exercise. The findings described in this review will help direct research into novel targets for the treatment of AD and develop customized exercise therapy for individuals of different ages, genders, and health conditions.

Key words: Alzheimer’s disease, amyloid beta, central nervous system, exerkine, neurodegeneration, neuroinflammation, neuroprotection, oxidative stress, physical exercise, Tau protein