Remyelination

[1] The process creates a thinner myelin sheath than normal, but it helps to protect the axon from further damage, from overall degeneration, and proves to increase conductance once again.

[3] Remyelination is activated and regulated by a variety of factors surrounding lesion sites that control the migration and differentiation of Oligodendrocyte Precursor Cells.

One way this process can be traced is by following different protein activation sequences which have shown just how quickly remyelination begins after injury (within a few of days).

Cytokines mediate inflammatory responses that promote pathogen and debris clearance so that further tissue damage is avoided.

[6] When the ligands Jagged1 and Delta, produced by axons, neurons, and astrocytes, are stimulated and bind to the membrane, oligodendrocyte maturation is inhibited.

Possible genes involved inside this pathway are TCF4 and OLIG2 which are both expressed in high amounts in areas where remyelination has failed from demyelinating diseases.

In a mouse model, it has been shown that testosterone, acting through the androgen receptor (AR), is important in remyelination by oligodendrocytes.

[13][14] Those same authors note that the AR evolved from a duplicated gene coincidentally with the development of myelin in jawed vertebrates.

Due to the wide variety of these factors it is difficult to study specifically but understanding can be big in treating demyelinating diseases.

There are a variety of types of these receptors, but a majority of them tend to increase, especially in the chronic stages of demyelinating diseases, suggesting that they may be involved with remyelination failure.

[18] Understanding completely the inhibiting and promoting factors of OPCs seems to be the key in battling demyelinating diseases such as multiple sclerosis that cause remyelination to fail.

The demyelinating disease attacks the myelin of axons in the central nervous system through autoimmune defects.

[1] As axons are left bare, without myelin, their conduction velocity goes down due to a lack in increased potential between the Nodes of Ranvier.

[1][7][11] Using antibodies to halt or promote certain parts of these pathways could be possible therapies to help increase OPC differentiation.

[20] Clemastine, an antihistamine drug, has been studied for its potential to possibly promote remyelination and myelin repair in conditions like multiple sclerosis (MS).

[23][24] However, a clinical trial (TRAP-MS) was halted in early 2024 after researchers found the disability progression was occurring at a significantly faster rate than anticipated in three participants with MS receiving clemastine.

New pathways are being discovered constantly in the areas of gene regulation, antibody use as antagonists, and promotion of stem cells to differentiate.

[1][18] One of the biggest difficulties of studying demyelinating diseases and thus remyelination is that it takes place in the central nervous system.

Studying remyelination most thoroughly would involve unethical and invasive experiments and observation on the human brain and spinal cord.