Question

Muscle atrophy is the loss of muscle mass with inactivity or disease. But what acutally causes the muscle to deteriorate? What causes the muscle fibers to shrink? What's the actual molecular/cellular mechanism causing muscle atrophy?

Answer 1

Muscle atrophy is defined as a decrease in the mass of the muscle, it can be a partial or complete wasting away of muscle.which makes the affected one harder to move arms and legs.

The main reason for muscle wasting is a lack of physical activity(disuse). This can also happen when a disease or injury makes it difficult or impossible for patient to move an arm or leg. some medications can also induce muscle atrophy by increasing break-down of muscle proteins, Ex : Glucocorticoids.

Muscle Deterioration :

During atrophy, there is a down-regulation of protein synthesis pathways, and an activation of protein degradation. The particular protein degradation pathway which seems to be responsible for much of the muscle loss is the ATP-dependentubiquitin/proteasome pathway.

Shrinkage of muscle fibres:

Actually, there are two types of muscle atrophy to be concerned with, one more severe than the other. The first type is called ‘disuse atrophy’ while the other is referred to as ‘neurogenic(Denervation) atrophy,’

In Neurogenic or denervation atropy, The motor neuron exerts a trophic influence on muscle. This influence is mediated by induced contractions and by chemical substances (trophic factors) released at the synapse, which influence protein synthesis in muscle. Myofibers that lose their innervation become angular and shrink.

molecular/cellular mechanism causing muscle atrophy :

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 of protein degradation.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-dependentubiquitin/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 it 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.