PathophysiologyMuscle atrophy occurs by a change in the normal balance between protein synthesis and protein degradation. During atrophy, there is a down-regulation of protein synthesis pathways, and an activation protein degradation.[1] The particular protein degradation pathway which seems to be responsible for much of the muscle loss seen in a muscle undergoing atrophy is the ATP-dependent ubiquitin/proteasome pathway. In this system, particular proteins are targeted for destruction by the ligation of at least four copies of a small peptide called ubiquitin onto a substrate protein. When a substrate is thus "poly-ubiquitinated", it is targeted for destruction by the proteasome. Particular enzymes in the ubiquitin/proteasome pathway allow ubiquitination to be directed to some proteins but not others - specificity is gained by coupling targeted proteins to an "E3 ubiquitin ligase". Each E3 ubiquitin ligase binds to a particular set of substrates, causing their ubiquitination.The change in synthesis during atrophy is called hypertrophy.[clarification needed]Potential treatmentMuscle atrophy can be opposed by the signaling pathways which induce muscle hypertrophy, or an increase in muscle size. Therefore one way in which exercise induces an increase in muscle mass is to downregulate the pathways which have the opposite effect.One important rehabilitation tool for muscle atrophy includes the use of functional electrical stimulation to stimulate the muscles. This has seen a large amount of success in the rehabilitation of paraplegic patients.[2]Since the absence of muscle-building amino acids can contribute to muscle wasting (that which is torn down must be rebuilt with like material), amino acid therapy may be helpful for regenerating damaged or atrophied muscle tissue. The branched-chain amino acids or BCAAs (leucine, isoleucine, and valine) are critical to this process, in addition to lysine and other amino acids.In severe cases of muscular atrophy, the use of an anabolic steroid such as methandrostenolone is administered to patients as a potential cure. A novel class of drugs, called SARM (selective androgen receptor modulators) are being investigating with promising results. They would have fewer side-effects, while still promoting muscle and bone tissue growth and regeneration. These claims are, however, yet to be confirmed in larger clinical trials.