Muscular Dystrophies and Cancer Cachexia: Similarities in Chronic Skeletal Muscle Degeneration

Journal of Functional Morphology and Kinesiology

Berardi, Emanuele¹ 

关键词: muscular dystrophies;    muscle degeneration;    inflammation;    cancer cachexia;    dystrophin glycoprotein complex;   

DOI  :  10.3390/jfmk2040039

学科分类：力学，机械学

来源: mdpi

【 摘 要 】

Muscular dystrophies (MDs) are inheritable diseases caused by mutations in specific genes encoding muscle proteins and characterized by progressive muscle wasting and weakness. MDs are classified into nine main categories, encompassing approximately 30 different diseases. Duchenne muscular dystrophy and Becker muscular dystrophy (DMD and BMD) are the most commonly diagnosed neuromuscular disorders, affecting respectively ~1/3500 and 3–6/100,000 male infants worldwide. DMD is characterized by absence of dystrophin function due to complete loss of expression or to the presence of a non-functional dystrophin protein in muscle tissue, while a semi-functional dystrophin isoform is typically present in BMD. Lack of dystrophin function in MDs induces myofiber damage, causing persistent cycles of degeneration/regeneration, exhaustion of regenerative potential and fibrosis, and resulting in muscle degeneration. Cancer cachexia is a multifactorial syndrome characterized by severe body weight loss and muscle degenerative atrophy. Up to 80% of cancer patients show cachexia, and the syndrome has been estimated to cause ~2 million of deaths per year. This cancer-related muscle wasting is mediated by pro-inflammatory cytokines and tumor-released mediators able to activate specific catabolic pathways in muscle tissue. MDs and cancer-associated cachexia (CAC) share some peculiar features, including systemic and muscle-specific inflammation, alteration of myogenic potential, ultrastructural abnormalities, and dysfunction of the dystrophin glycoprotein complex (DCG). This review focuses on the pathophysiological comparison between these two chronic muscle degenerative conditions and discusses the most relevant and promising therapeutic strategies considered so far.

【 授权许可】

CC BY