Therapeutic approaches for muscle wasting disorders.
Muscle wasting and weakness are common in many disease states and conditions including aging, cancer cachexia, sepsis, denervation, disuse, inactivity, burns, HIV-acquired immunodeficiency syndrome (AIDS), chronic kidney or heart failure, unloading/microgravity, and muscular dystrophies. Although the maintenance of muscle mass is generally regarded as a simple balance between protein synthesis and protein degradation, these mechanisms are not strictly independent, but in fact they are coordinated by a number of different and sometimes complementary signaling pathways. Clearer details are now emerging about these different molecular pathways and the extent to which these pathways contribute to the etiology of various muscle wasting disorders. Therapeutic strategies for attenuating muscle wasting and improving muscle function vary in efficacy. Exercise and nutritional interventions have merit for slowing the rate of muscle atrophy in some muscle wasting conditions, but in most cases they cannot halt or reverse the wasting process. Hormonal and/or other drug strategies that can target key steps in the molecular pathways that regulate protein synthesis and protein degradation are needed. This review describes the signaling pathways that maintain muscle mass and provides an overview of some of the major conditions where muscle wasting and weakness are indicated. The review provides details on some therapeutic strategies that could potentially attenuate muscle atrophy, promote muscle growth, and ultimately improve muscle function. The emphasis is on therapies that can increase muscle mass and improve functional outcomes that will ultimately lead to improvement in the quality of life for affected patients.
Lynch
Gordon S
GS
Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria 3010, Australia. gsl@unimelb.edu.au
Schertzer
Jonathan D
JD
Ryall
James G
JG
D016207:Cytokines / Q000627:therapeutic use; D015444:Exercise; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism*; D009133:Muscular Atrophy / Q000503:physiopathology / Q000628:therapy; D009135:Muscular Diseases / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D044623:Nutrition Therapy; D014176:Protein Biosynthesis / Q000502:physiology; D011788:Quality of Life; D015398:Signal Transduction / Q000502:physiology*; D013566:Sympathomimetics / Q000627:therapeutic use
D016207:Cytokines; D006728:Hormones; D009124:Muscle Proteins; D013566:Sympathomimetics