Molecular mechanisms involved in remyelination

Molecular mechanisms involved in remyelination

In vertebrates, axons extending from nerve cells are covered by insulating sheets called the myelin sheath, made with the cell membranes of oligodendrocytes, enabling fast electrical signaling through saltatory conduction.

Normally, myelin is repaired, even if damaged, but the mechanism that controls remyelination was not well understood. In addition, in demyelinating diseases such as multiple sclerosis, the myelin sheath does not recover from damage and gets worse, finally leading to symptoms such as vision loss, limb numbness, and movement disorders.

Researchers performed a detailed examination of the remyelinating process of damaged myelin using disease model mice. Their results show that a growth factor called pleiotrophin (PTN) is secreted from nerve axons injured by demyelination, and this PTN inhibits the function of the receptor molecule PTPRZ of oligodendrocyte precursor cells, stimulating cellular differentiation into oligodendrocytes which form the myelin sheath, thereby promoting remyelination.

Oligodendrocyte differentiation was augmented in a primary culture of oligodendrocyte-lineage cells from wild-type mice in response to PTN. In contrast, these cells from Ptprz-deficient mice showed higher oligodendrocyte differentiation without PTN and differentiation was not enhanced by its addition. They further demonstrated that PTN treatment increased the tyrosine phosphorylation of p190 RhoGAP, a PTPRZ substrate.

The results of this research were published in 'The Journal of Neuroscience'.