RESUMEN
Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation and demyelination in the central nervous system (CNS) with subsequent axonal and neuronal degeneration. These changes are associated with a broad range of symptoms including skeletal muscle dysfunction. Importantly, musculoskeletal impairments manifest in various ways, compromise the quality of life and often precede the later development of mobility disability. As current standard disease modifying therapies for MS predominantly act on neuroinflammation, practitioners and patients face an unmet medical need for adjunct therapies specifically targeting skeletal muscle function. This review is intended to detail the nature of the skeletal muscle dysfunctions common in people with MS (pwMS), describe underlying intramuscular alterations and outline evidence-based therapeutic approaches. Particularly, we discuss the emerging role of aerobic and resistance exercise for reducing the perception of fatigue and increasing muscle strength in pwMS. By integrating the most recent literature, we conclude that both exercise interventions should ideally be implemented as early as possible as they can address MS-specific muscle impairments. Aerobic exercise is particularly beneficial for pwMS suffering from fatigue and metabolic impairments, while resistance training efficiently counters muscle weakness and improves the perception of fatigue. Thus, these lifestyle interventions or possible pharmacological mimetics have the potential for improving the general well-being and delaying the functional declines that are relevant to mobility.
RESUMEN
Musculoskeletal diseases are a leading contributor to mobility disability worldwide. Since the majority of patients with musculoskeletal diseases present with associated muscle weakness, treatment approaches typically comprise an element of resistance training to restore physical strength. The health-promoting effects of resistance exercise are mediated via complex, multifarious mechanisms including modulation of systemic and local inflammation. Here we investigated whether targeted inhibition of the chemerin pathway, which largely controls inflammatory processes via chemokine-like receptor 1 (CMKLR1), can improve skeletal muscle function. Using genetically modified mice, we demonstrate that blockade of CMKLR1 transiently increases maximal strength during growth, but lastingly decreases strength endurance. In-depth analyses of the underlying long-term adaptations revealed microscopic alterations in the number of Pax7-positive satellite cells, as well as molecular changes in genes governing myogenesis and calcium handling. Taken together, these data provide evidence of a critical role for CMKLR1 in regulating skeletal muscle function by modulating the regenerative and contractile properties of muscle tissue. CMKLR1 antagonists are increasingly viewed as therapeutic modalities for a variety of diseases (e.g., psoriasis, metabolic disorders, and multiple sclerosis). Our findings thus have implications for the development of novel drug substances that aim at targeting the chemerin pathway for musculoskeletal or other diseases.