Scientists from Singapore have uncovered the crucial role of a transporter protein in regulating the brain cells responsible for protecting nerves with myelin sheaths. This discovery, reported by researchers at Duke-NUS Medical School and the National University of Singapore, could potentially mitigate the negative effects of aging on the brain.
Myelin sheaths are insulating membranes that surround nerves and ensure the rapid and efficient transmission of electrical signals throughout the body’s nervous system. When these myelin sheaths become damaged, nerves can lose their functionality, leading to neurological disorders. As individuals age, myelin sheaths may naturally deteriorate, resulting in the decline of physical and mental abilities in the elderly.
Dr. Sengottuvel Vetrivel, Senior Research Fellow at Duke-NUS’ Cardiovascular & Metabolic Disorders (CVMD) Programme and the lead investigator of the study, explained that the loss of myelin sheaths is a part of the normal aging process and is also observed in neurological diseases such as multiple sclerosis and Alzheimer’s disease. Developing therapies to enhance myelination, the formation of myelin sheaths, is crucial to combat the difficulties caused by declining myelination.
To advance the development of such therapies, the researchers aimed to understand the role of a protein called Mfsd2a. This protein transports lysophosphatidylcholine (LPC), a lipid containing an omega-3 fatty acid, into the brain as a part of the myelination process. Genetic defects in the Mfsd2a gene have been linked to significantly reduced myelination and a birth defect called microcephaly, which causes an abnormally small head in infants.
Through preclinical models, the team demonstrated that removing Mfsd2a from precursor cells that mature into myelin-producing cells in the brain resulted in deficient myelination after birth. Further investigations, including single-cell RNA sequencing, revealed that the absence of Mfsd2a led to a reduction in fatty acid molecules, particularly omega-3 fats, within the precursor cells. This, in turn, prevented the maturation of these cells into oligodendrocytes, which are responsible for producing myelin.
Professor David Silver, the senior author of the study and Deputy Director of the CVMD Programme, explained that the study indicates the crucial role of LPC omega-3 lipids in directing oligodendrocyte development, which is vital for brain myelination. This discovery opens up potential avenues for developing therapies and dietary supplements based on LPC omega-3 lipids to preserve myelin in the aging brain and potentially treat patients with neurological disorders caused by reduced myelination.
Previously, Prof. Silver and his team discovered Mfsd2a and worked with other researchers to determine the function of LPC lipids in the brain and other organs. This new research provides further insights into the importance of lipid transport for the development of oligodendrocyte precursor cells.
Prof. Silver stated that their next goal is to conduct preclinical studies to determine if dietary LPC omega-3 can aid in the re-myelination of damaged axons in the brain. They hope that supplements containing these fats can help maintain or improve brain myelination and cognitive function during the aging process.
Professor Patrick Casey, Senior-Vice Dean for Research, commended Prof. Silver’s dedication in investigating the broad role of Mfsd2a since its discovery, highlighting the potential for treating not only the aging brain but also other organs where this protein plays a role. He expressed excitement at watching Prof. Silver and his team shape our understanding of the functions of these specialized lipids through their various discoveries.