TMEM10 in Demyelinated MS Lesions May Contribute to Remyelination, Study Suggests

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by Jonathan Grinstein |

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A protein that promotes nervous system repair through remyelination — the creation of myelin, the protective sheath around nerve cells — in mice also is found in remyelinating plaques in brains of multiple sclerosis (MS) patients, new research shows.

This protein potentially represents a new therapeutic target in demyelinating disorders like MS.

The research article reporting the findings is titled “TMEM10 Promotes Oligodendrocyte Differentiation and is Expressed by Oligodendrocytes in Human Remyelinating Multiple Sclerosis Plaques,” and was published in the journal Nature Scientific Reports.

In the central nervous system, myelin is produced by cells called oligodendrocytes. Remyelination occurs through oligodendrocyte differentiation — when oligodendrocyte precursor cells (OPCs) grow to form oligodendrocytes that can create new myelin sheaths on demyelinated nerve projections.

OPCs in the adult nervous systems initially are able to differentiate and remyelinate demyelinated regions. However, remyelination efficiency decreases as MS progresses, likely due to impairment of OPC differentiation.

Currently, there are no approved therapies that can improve remyelination as part of the nervous system repair. This is partly because the mechanisms regulating oligodendrocyte differentiation remain to be discovered, and a comprehensive picture of how myelination occurs during development is unclear. That is why identifying these mechanisms is crucial.

Transmembrane Protein 10, or TMEM10 (also known as Opalin), is a mammalian-specific gene found in oligodendrocytes. Studies have suggested that TMEM10 may influence OPC differentiation and myelination during development. However, the role of TMEM10 in remyelination and nervous system repair in mammals is unknown.

For these reasons, researchers from McGill University, in Canada, studied the role of TMEM10 in mouse nervous system development, oligodendrocyte differentiation, and myelination. They also investigated the role of TMEM10 in MS lesions in human brain samples.

Researchers first detected TMEM10 protein during postnatal brain development in mice, with levels continuing to increase during maturation.

The team saw that without TMEM10, primary OPCs taken directly from mouse brains differentiated into oligodendrocytes with an abnormal shape and structure, as well as reduced levels of myelin-related proteins.

In contrast, increasing TMEM10 in an OPC cell line cultured in the laboratory made the cells look more mature, and to develop as healthy oligodendrocytes. Increased levels of myelin-associated gene products were seen in these cells, whereas blocking TMEM10 in differentiating cultured OPCs decreased myelin gene product levels.

To investigate the possibility that TMEM10 may play an important role during remyelination in MS lesions, researchers also examined brain samples from six MS patients. In five out of six lesions (four lesions with signs of remyelination, and one lesion without), researchers detected TMEM10-positive oligodendrocytes.

Overall, the findings “provide evidence that TMEM10 promotes oligodendrocyte precursor cell differentiation, and suggest that TMEM10 expressed in demyelinated MS lesions may contribute to remyelination,” the researchers wrote.

“Further investigation will be necessary to define the functional contribution of TMEM10 to remyelination, and address the potential of TMEM10 as a novel therapeutic target in multiple sclerosis,” the team concluded.

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