Pathophysiology

Muscle 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 ATPdependent 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 treatment
Muscle 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.