Transporter protein crucial for protecting nerves in the brain with implications for ageing and neurological disorders

A team of scientists from Singapore has made a significant discovery about a crucial transporter protein that regulates brain cells responsible for safeguarding nerves with myelin sheaths. According to the study, published in the Journal of Clinical Investigation and conducted by researchers from Duke-NUS Medical School and the National University of Singapore, the findings could have practical applications in reducing the negative effects of ageing on the brain.

Myelin sheaths, a protective membrane that enwraps nerves, play a critical role in ensuring the efficient and rapid transmission of electrical signals throughout the nervous system. Neurological disorders can arise when the myelin sheath becomes damaged and nerve functionality is lost. As people age, their myelin sheaths can naturally degenerate, leading to the physical and mental decline commonly associated with ageing.

Dr. Sengottuvel Vetrivel, Senior Research Fellow with Duke-NUS’ Cardiovascular & Metabolic Disorders Programme, and the study’s lead investigator, stated that the loss of myelin sheaths is a natural part of the ageing process and occurs in neurological conditions like Alzheimer’s disease and multiple sclerosis. Developing therapies to enhance myelination or the formation of the myelin sheath is critical to alleviate the challenges caused by deteriorating myelination.

To advance the development of such therapies, the researchers explored the function of Mfsd2a, a protein that transports lysophosphatidylcholine (LPC), a lipid that contains omega-3 fatty acids, into the brain as part of the myelination process. Previous research has indicated that genetic abnormalities in the Mfsd2a gene lead to a significant reduction in myelination and microcephaly, a congenital condition that results in an abnormally small head size.

Through preclinical models, the research team discovered that the removal of Mfsd2a from precursor cells, which transform into myelin-producing oligodendrocytes in the brain, resulted in deficient myelination after birth. Further investigations, including single-cell RNA sequencing, revealed that the lack of Mfsd2a caused a reduction in the pool of fatty acid molecules, especially omega-3 fats, in the precursor cells. As a result, these cells could not mature into oligodendrocytes that produce myelin.

Professor David Silver, the Deputy Director of the CVMD Programme and senior author of the study, stated that their research shows that LPC omega-3 lipids act as vital factors within the brain to direct the development of oligodendrocytes, a process critical for brain myelination. This discovery suggests potential new avenues to develop therapies and dietary supplements based on LPC omega-3 lipids that could help retain myelin in ageing brains and treat patients with neurological disorders resulting from reduced myelination.

Prior to this research, Professor David Silver and his team had previously discovered Mfsd2a and collaborated with other research groups to determine the function of LPC lipids in the brain and other organs. The current study offers additional insights into the significance of lipid transport for the development of oligodendrocyte precursor cells.

Prof Silver explained that they now plan to carry out preclinical studies to investigate whether dietary LPC omega-3 can aid in the re-myelination of damaged axons in the brain. He hopes that supplements containing these fats can help maintain or enhance brain myelination and cognitive function during ageing.

Professor Patrick Casey, the Senior-Vice Dean for Research, praised Prof Silver for his dedication to investigating the far-reaching role of Mfsd2a and the many possible ways of treating not just the ageing brain but also other organs in which the protein is involved. He added that Prof Silver and his team’s numerous discoveries have been instrumental in shaping our understanding of the functions of these specialised lipids.

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