The mechanisms of myelination

The defects in synthesis and maintenance of myelin result in demyelinating neuropathies. A family of Neuregulin1 (NRG1) proteins is involved in myelination in both peripheral and central nervous systems (PNS and CNS).

Membrane-bound NRG1 are cleaved by secretases. Upon cleavage, type I and type II NRG1 are released from the neuronal membrane. Type III NRG1 remains tethered on the axonal surface and acts as a juxtacrine signal, controlling the formation of myelin in the nerves. Secretases also induce the expression of other molecules that promote myelin formation and maintenance in the nerves.

With EU funding, the project 'Role of secretases in myelination' (SECRETASES & MYELIN) aimed to investigate the role of secretases in PNS myelination. A combination of cell culture techniques and in vivo animal models was used to study the molecular mechanisms regulating PNS myelin formation and maintenance.

The results of the study suggest that NRG1 type III controls myelination in multiple ways. Obtained data support the existence of a novel pathway whose modulation could be beneficial for the treatment of peripheral demyelinating neuropathies.

Elucidating the mechanisms controlling NRG1 type III activity and identifying the role of secretases provided important insights into the mechanisms controlling regulation of myelination. Understanding the mechanisms of development of demyelinating diseases aids future development of therapeutic approaches to improve the quality of life of individuals affected by them.