Abstract
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.
Highlights
Muscular dystrophies (MDs) and cancer-associated cachexia (CAC) are debilitating degenerative conditions causing loss of both muscle mass and function [1]
This study showed that besides being hallmark of MDs, Dystrophin Glycoprotein Complex (DGC) dysfunction is an important pathological characteristic of cancer cachexia [15]
Dysfunctions in DGC similar to those observed in MDs have been identified in cancer-related muscle wasting, suggesting that myofiber damage might proceed via common mechanisms shared by these two different muscle degenerative conditions [15]
Summary
Muscular dystrophies (MDs) and cancer-associated cachexia (CAC) are debilitating degenerative conditions causing loss of both muscle mass and function [1]. The most common muscular dystrophies, Duchenne muscular dystrophy (DMD) and the Becker muscular dystrophy (BMD), are caused by mutations in the DMD gene encoding the 427 kD structural protein called dystrophin [2]. Because of the different aetiology between MDs and CAC (i.e., genetic vs cancer-associated muscle degenerative condition, respectively), such diseases are diagnosed using different criteria to evaluate the extent of muscle degeneration. 2. Alterations in Dystrophin Glycoprotein Complex (DGC) in MDs (Muscular Dystrophies) and CAC (Cancer-Associated Cachexia). Mutations in genes encoding specific proteins of the DGC or their posttranslational defects might alter the function of the complex, resulting in sarcolemma damage. This study showed that besides being hallmark of MDs, DGC dysfunction is an important pathological characteristic of cancer cachexia [15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
