The human brain is a complex and highly protected organ, guarded by a specialized layer of cells called the blood-brain barrier. This barrier acts as a security system, preventing potentially harmful substances in the bloodstream from entering the brain. However, this protective mechanism also poses a challenge for delivering drugs to treat neurological disorders like Alzheimer’s and stroke. Now, a landmark discovery by researchers at the University of Queensland’s Institute for Molecular Bioscience may provide a solution to this problem.
Published in the journal Nature, researchers have identified molecular doorways that could be exploited to transport drugs across the blood-brain barrier. These doorways are actually proteins called FLVCR2, which are responsible for shuttling an essential nutrient called choline into the brain.
Choline is a vitamin-like compound that plays a crucial role in many bodily functions, especially in brain development.
“We need to consume 400-500 milligrams of choline per day to support cell regeneration, gene expression regulation, and for sending signals between neurons,” says lead study author Dr. Rosemary Cater, from University of Queensland’s Institute for Molecular Bioscience, in a media release.
Despite its importance, little was known about how dietary choline manages to cross the blood-brain barrier — until now. Dr. Cater’s research has revealed that choline sits snugly in a cavity within the FLVCR2 protein as it travels across the barrier, held securely in place by a cage of protein residues.
To visualize this intricate molecular process, researchers employed high-powered cryo-electron microscopes. These sophisticated tools allowed them to see exactly how choline binds to FLVCR2 at an atomic level.
“This is critical information for understanding how to design drugs that mimic choline so that they can be transported by FLVCR2 to reach their site of action within the brain,” explains Dr. Cater. “These findings will inform the future design of drugs for diseases such as Alzheimer’s and stroke.”
While the blood-brain barrier is essential for protecting the brain from harmful toxins, it also presents a major obstacle for delivering therapeutic drugs to treat neurological conditions. Many promising drug candidates that show potential in laboratory tests fail to reach their target sites in the brain when administered to patients. By harnessing the FLVCR2 transporter as a molecular shuttle, researchers may be able to overcome this hurdle and develop more effective treatments for brain disorders.
The discovery also underscores the importance of including choline-rich foods in our diets. Eggs, vegetables, meat, nuts, and beans are all excellent dietary sources of this essential nutrient. Ensuring an adequate intake of choline not only supports overall brain health but may also optimize the function of the FLVCR2 transporters.
In the future, medications that mimic choline’s structure could potentially hitchhike on the FLVCR2 transporter, crossing the blood-brain barrier to reach their intended targets within the brain. This could open up new possibilities for treating a wide range of neurological conditions, from neurodegenerative diseases like Alzheimer’s to acute brain injuries like stroke.
