AsianScientist (Jun. 1, 2015) – Research led by a Duke-NUS Graduate Medical School Singapore (Duke-NUS) scientist has proved that certain special fats found in blood are essential for human brain growth and function.
The studies, published in Nature Genetics and co-led by Duke-NUS Associate Professor David Silver, showed that mutations in the protein Mfsd2a causes impaired brain development in humans. Mfsd2a is the transporter in the brain for a special type of fat called lysophosphatidylcholines (LPCs)—composed of essential fatty acids like omega-3. These studies show, for the first time, the crucial role of these fats in human brain growth and function.
In the first study, two families in Libya and Egypt with Mfsd2a mutations were identified with severely reduced brain size, or microcephaly. Their mutations eliminated Mfsd2a’s ability to transport LPCs, which meant not enough LPCs were absorbed by the brain. In these families, children affected by these mutations died between one and six years of age.
In a second, separate study, a family in North Pakistan was found to have another type of mutation in the Mfsd2a gene which reduced its transport activity. The individuals with this mutation also had microcephaly, but in this case it was not lethal. However, they did have intellectual disabilities, impaired control of their limbs and absent speech. Like the first study, findings highlight the importance of LPCs in brain development and function.
In 2014, Silver published a landmark study in Nature which served as a basis for these two studies. He and his team discovered that Mfsd2a is the transporter for LPCs. Prior to this breakthrough, LPCs were known to be found at high concentrations in our blood but their function was a mystery. Also, while it was previously believed the brain made all the fat it needed, Silver’s research showed that LPCs are transported there from the blood past the blood-brain barrier.
“Our work confirms the essential role of LPCs in brain development and function in humans and indicates that brain uptake of LPCs during foetal development and in adult life is important,” said Silver, based in the Cardiovascular and Metabolic Disorders Programme at Duke-NUS.
“Now we are studying the functions of LPCs in the brain and the implications for application are very exciting. We might be able to develop therapeutics in the future that could prevent and treat neurological disorders and improve brain growth and function. We may even be able to target better brain nutrition for babies, mothers and the aged.”
The articles can be found at:
Guemez-Gamboa et al. (2015) Inactivating Mutations in MFSD2A, Required for Omega-3 Fatty Acid Transport in Brain, Cause a Lethal Microcephaly Syndrome.
Alakbarzade et al. (2015) A Partially Inactivating Mutation in the Sodium-dependent Lysophosphatidylcholine Transporter MFSD2A Causes a Non-lethal Microcephaly Syndrome.
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Source: Duke-NUS Graduate Medical School Singapore.
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