Sandbox Reserved 1092: Difference between revisions

- '''Follistatin''' is able to for complexes with Myostatin, enabling the inhibition of the Myostatin’s action on muscular development.

Myostatin <ref name="edumont">Université de Montpellier. Physiologie et médecien fondamentale du coeur et des muscles : myostatine. [https://u1046.edu.umontpellier.fr/163-2/abrege-des-proteines-musculaires/myostatine/]</ref> is a protein that has a control over muscle development: it is a negative regulator of squeletics muscles. It has a very important role during the development of the animals but also during its whole life. It is a very important protein that is very conserved from zebra fish to humans <ref name="patho">PMID:19412331</ref> and so it has to be very well regulated. Indeed, there are many ways that regulates the action of this protein and at many scales.

It is a grown factor<ref name="patho"/> that is implicated into muscle development in mammals. Myostatin can transmit a message to the nucleus that will promote a gene that lead to the production of ubiquitin. Ubiquitin is a signal of degradation so muscle cells will be destroyed. Indeed, it reduce the mass of the muscle but it also reduces the quantity of [[Myosin]] <ref>Jeffrey L. Corden,David Tollervey. Cell Biology, Chapter 36 Motor Proteins.2017 [https://doi.org/10.1016/B978-0-323-34126-4.00036-0 DOI:10.1016/B978-0-323-34126-4.00036-0] </ref> which is very important for the cohesion of muscles and for movement. Indeed [[Myosin]] forms filament, and when [[Myosin]] filaments associate with [[Actin]] and consume [[ATP]] it produces muscle movement.

If the quantity of myosin is not well regulated in the human body, it could trigger many muscle related illnesses<ref name="disease">Sharma, M., McFarlane, C., Kambadur, R., Kukreti, H., Bonala, S. and Srinivasan, S. (2015), Myostatin: Expanding horizons. IUBMB Life, 67: 589-600. [ https://doi.org/10.1002/iub.1392 DOI:10.1002/iub.1392]</ref>, especially when there is too much myostatin, as heart disease, liver disease..

We can focus on the example of COPD (Chronic Obstructive Pulmonary Disease) which is a lunch disease. People suffering from this disease have difficulties to breathe because of an obstruction of airflow <ref name="disease"/> . Their muscles are not strong enough to help them to breathe the right way and it is called pulmonary cachexia. This disease is also characterized by many muscle complications into the whole body, including a global reduction of muscle mass. It has been proven that a high rate of myostatin quantity in human body can promote this disease.

Myostatin has also a role in many metabolisms as in blood glucose<ref name="disease"/>: indeed, the more myostatin you have, the more resistant to insulin you are. This could be link with Type 2 diabetes and so obesity because it is an inducer of Phosphotyrosine Interaction Domain containing 1 (PID1) protein [https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=DetailsSearch&Term=55022] in human muscle cells. Indeed, this protein is known for its role into insulin resistance development.

However, myostatin can also be a way to cure some disease:

If myostatin action is inhibited, researchers have noticed that muscular mass increases <ref name="edumont"/><ref name="patho"/>.Indeed, myostatin and particularly its inhibition can be a solution to cure muscle atrophy disease: let’s focus on the example of OPMD <ref> PMID:31066242</ref>, oculopharyngeal muscular dystrophy: This disease involves that the muscles affected show increased fibrosis and atrophy.This is a late-onset disease, affecting 1 people over 80000. It is characterized by dysphagia and ptosis but also limb weakness when the disease is at a very advanced stage. Researcher have noticed that the inhibition of myostatin, increased the muscle quantity and so it help to reduce the symptoms of OPMD.

In this case, a monoclonal antibiotic is injected to mice during 10 weeks and the results show that muscle strength and muscle fiber diameter increased and the expression of the markers of muscle fibrosis reduced. However, myostatin does not cure the disease because there was no change in intranuclear inclusion density which is a characteristic of OPMD spread, so, it only treats the symptom.

In other cases, it is also possible to introduce follistatin  <ref> PMID:19644449</ref> to block myostatin because they will form a complex and so it will stop myostatin actions.