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Discovery of a Lesser-Known Choline Transporter in the Brain Highlights Potential Therapeutic Avenue for Age-Related Cognitive Decline and Alzheimer's Disease

Monday, May 06, 2024

Researchers at the Yong Loo Lin School of Medicine at the National University of Singapore (NUS Medicine) have made an intriguing discovery regarding the orphan transporter known as Mfsd7c at the blood-brain barrier (BBB). They found that Mfsd7c acts not as an importer of choline into the brain from the bloodstream, as previously thought, but rather as an exporter of excess choline out of the brain. This unexpected finding challenges existing theories of choline metabolism and presents new possibilities for treating Alzheimer's disease and other neurological disorders.

To uncover this, the researchers injected a compound called lysophosphatidylcholine (LPC) into preclinical models. This caused the release of choline into the brain, allowing them to trace its source from the blood. They observed that labeled choline, derived from blood LPC, accumulated in the brains of preclinical models when Mfsd7c protein was inhibited at the BBB. Surprisingly, the brain's lipid profile remained unaffected, indicating that excess choline from LPC was being expelled from the brain via Mfsd7c at the BBB.

Additionally, targeting Mfsd7c in preclinical models led to increased levels of choline and acetylcholine in the brain. This suggests that targeting Mfsd7c could potentially elevate choline and acetylcholine levels in elderly individuals and Alzheimer's patients, who often exhibit decreased acetylcholine levels in the brain. Since choline is crucial for acetylcholine synthesis, which is involved in memory, learning, and muscle control, this finding opens new avenues for therapeutic strategies in Alzheimer's disease.

Choline, an essential nutrient for brain development and function, plays a vital role in regulating memory, mood, and muscle control. Given that the human brain consists of about two-thirds lipids, including choline-containing lipids, understanding its metabolism is key to unraveling neurological disorders.

The research team is now focused on harnessing their discovery to develop drugs that target Mfsd7c in the brain, aiming to translate their findings into tangible therapeutic interventions for neurological disorders. This groundbreaking study marks a significant advancement in our comprehension of brain metabolism and offers hope for the development of effective treatments for Alzheimer's disease and related conditions.



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