Hersenen van het zich ontwikkelende preklinische model met gemyeliniseerde axonen (weergegeven in groen). Wetenschappers uit Singapore hebben de cruciale rol ontdekt van een transporteiwit, Mfsd2a, bij het reguleren van hersencellen die myeline-omhulsels in stand houden, het isolerende membraan dat zenuwen omhult. Deze resultaten gepubliceerd in Tijdschrift voor klinisch onderzoekHet kan de effecten van veroudering op de hersenen helpen verminderen. Mfsd2a transporteert lysofosfatidylcholine (LPC), een lipide dat omega-3-vetzuren bevat, naar de hersenen voor myelogenese. Krediet: Dr. Vetrivel Sengotuvil
Onderzoekers hebben ontdekt dat het transporteiwit Mfsd2a essentieel is voor het reguleren van hersencellen die de myeline-omhulsels in stand houden die de zenuwen beschermen. Deze ontdekking kan helpen de effecten van veroudering op de hersenen te verminderen en kan leiden tot behandelingen voor neurologische aandoeningen veroorzaakt door verminderde myelogenese.
Wetenschappers uit Singapore hebben de cruciale rol aangetoond die een speciaal transporteiwit speelt bij het reguleren van hersencellen die ervoor zorgen dat zenuwen worden beschermd door omhulsels die myeline-omhulsels worden genoemd. De bevindingen, gepubliceerd door onderzoekers van de Duke-NUS Medical School en de National University of Singapore in Tijdschrift voor klinisch onderzoekHet kan helpen de schadelijke effecten van veroudering op de hersenen te verminderen.
Myeline-omhulsels, een isolerend membraan dat zenuwen omringt, vergemakkelijken de snelle en efficiënte geleiding van elektrische signalen door het zenuwstelsel van het lichaam. Wanneer de myelineschede beschadigd is, kunnen zenuwen hun vermogen om te functioneren verliezen en neurologische aandoeningen veroorzaken. Met het ouder worden kunnen myeline-omhulsels van nature beginnen te verslechteren, waardoor oudere mensen hun fysieke en mentale vermogens verliezen.
Verlies van myeline-omhulsels treedt op tijdens het normale verouderingsproces en bij neurodegeneratieve ziekten, zoals multiple sclerose en[{” attribute=””>Alzheimer’s disease,” said Dr. Sengottuvel Vetrivel, Senior Research Fellow with Duke-NUS’ Cardiovascular & Metabolic Disorders (CVMD) Program and lead investigator of the study. “Developing therapies to improve myelination—the formation of the myelin sheath—in aging and disease is of great importance to ease any difficulties caused by declining myelination.”
To pave the way for developing such therapies, the researchers sought to understand the role of Mfsd2a, a protein that transports lysophosphatidylcholine (LPC)—a lipid that contains an omega-3 fatty acid—into the brain as part of the myelination process. From what is known, genetic defects in the Mfsd2a gene leads to significantly reduced myelination and a birth defect called microcephaly, which causes the baby’s head to be much smaller than it should be.
Dr. Sengottuvel Vetrivel (left) and Prof David Silver (right). Credit: Duke-NUS Medical School
In preclinical models, the team showed that removing Mfsd2a from precursor cells that mature into myelin-producing cells—known as oligodendrocytes—in the brain led to deficient myelination after birth. Further investigations, including single-cell RNA sequencing, demonstrated that Mfsd2a’s absence caused the pool of fatty acid molecules—particularly omega-3 fats—to be reduced in the precursor cells, preventing these cells from maturing into oligodendrocytes that produce myelin.
“Our study indicates that LPC omega-3 lipids act as factors within the brain to direct oligodendrocyte development, a process that is critical for brain myelination,” explained Professor David Silver, the senior author of the study and Deputy Director of the CVMD Program. “This opens up potential avenues to develop therapies and dietary supplements based on LPC omega-3 lipids that might help retain myelin in the aging brain—and possibly to treat patients with neurological disorders stemming from reduced myelination.”
Previously, Prof Silver and his lab discovered Mfsd2a and worked closely with other teams to determine the function of LPC lipids in the brain and other organs. The current research provides further insights into the importance of lipid transport for oligodendrocyte precursor cell development.
“We’re now aiming to conduct preclinical studies to determine if dietary LPC omega-3 can help to re-myelinate damaged axons in the brain,” added Prof Silver. “Our hope is that supplements containing these fats can help to maintain—or even improve—brain myelination and cognitive function during aging.”
“Prof Silver has been relentless in investigating the far-reaching role of Msdf2a ever since he discovered this important lipid transport protein, alluding to the many possible ways of treating not only the aging brain but also other organs in which the protein plays a role,” said Professor Patrick Casey, Senior-Vice Dean for Research. “It’s exciting to watch Prof Silver and his team shape our understanding of the roles that these specialized lipids play through their many discoveries.”
Reference: “Deficiency in the omega-3 lysolipid transporter Mfsd2a leads to aberrant oligodendrocyte lineage development and hypomyelination” by Vetrivel Sengottuvel, Monalisa Hota, Jeongah Oh, Dwight L. Galam, Bernice H. Wong, Markus R. Wenk, Sujoy Ghosh, Federico Torta and David L. Silver, 27 April 2023, The Journal of Clinical Investigation.
DOI: 10.1172/JCI164118
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