Physical Exercise-Induced Myokines in Neurodegenerative Diseases

Abstract

Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), are disorders characterized by progressive degeneration of the nervous system. Currently, there is no disease-modifying treatments for most NDs. Meanwhile, numerous studies conducted on human and animal models over the past decades have showed that exercises had beneficial effects on NDs. Inter-tissue communication by myokine, a peptide produced and secreted by skeletal muscles during exercise, is thought to be an important underlying mechanism for the advantages. Here, we reviewed studies about the effects of myokines regulated by exercise on NDs and their mechanisms. Myokines could exert beneficial effects on NDs through a variety of regulatory mechanisms, including cell survival, neurogenesis, neuroinflammation, proteostasis, oxidative stress, and protein modification. Studies on exercise-induced myokines are expected to provide a novel strategy for treating NDs, for which there are no adequate treatments nowadays. To date, only a few myokines have been investigated for their effects on NDs and studies on mechanisms involved in them are in their infancy. Therefore, future studies are needed to discover more myokines and test their effects on NDs.

Protocol for Exploring the Role of Irisin in the Enhancement of Spatial Learning Mediated by Aerobic Physical Exercise in Adult Mice

“…LeBlanc et al conclude that irisin levels increased significantly after APE, not RE, indicating a positive association between APE and irisin [10]. In addition to its role in PE, irisin is involved in delaying or suppressing neurodegeneration in the brain [11]. In mouse hippocampal lines, a proliferation assay was conducted to test cell proliferation as a direct result of irisin [11].…”

“…In addition to its role in PE, irisin is involved in delaying or suppressing neurodegeneration in the brain [11]. In mouse hippocampal lines, a proliferation assay was conducted to test cell proliferation as a direct result of irisin [11]. Results show that 50-100 nM of irisin increased cell proliferation by 80% compared to the control treatment line [11].…”

Exercise-induced modulation of myokine irisin in bone and cartilage tissue—Positive effects on osteoarthritis: A narrative review

“…Since the concept of myokines was introduced in 2003 (Pedersen and Febbraio, 2012), more than 300 myokines have been identified in the last 20 years, such as interleukin-6 (IL-6), interleukin-15 (IL-15), fibroblast growth factor 21 (FGF21), myostatin, among others, which also includes irisin. These muscle factors have been shown to be involved in adipose tissue, liver, bone (Trayhurn et al, 2011;Zymbal et al, 2019), central nervous system (Voss et al, 2019;Lee et al, 2021), and immune system (Flori et al, 2021). They play a role in driving browning of white fat (Lee et al, 2014), insulin-sensitive states (Lee et al, 2015), optimizing whole-body energy metabolism, preventing metabolic diseases, and playing a protective role in low-level inflammation on a systemic scale (Tanabe et al, 2017;Flori et al, 2021).…”

Effects of Exercise on Skeletal Muscle Pathophysiology in Huntington’s Disease

“…Exercise-induced CEUs, increased Orai1-dependent Ca 2+ entry to favor myoplasmic Ca 2+ dynamics, reducing muscle force decline during sustained activation [ 62 , 63 ]. Noteworthy, exercise supports the production and secretion of myokines by skeletal muscles [ 64 ], such as BDNF, which promotes HD mice’s motor functions and survival rate, by counteracting brain atrophy [ 65 , 66 ]. However, the effects of physical exercise on HD animal models reported controversial data.…”