SCI Rep: use LAT1 to deliver drugs more effectively in the brain

October 25, 2019 / Biovalley BIOON / -- according to a new study by the University of East Finland, the highly expressed LAT1 in the brain can improve the distribution of drug molecules in the brain By temporarily transforming the drug molecules into prodrugs, these derivatives can use LAT1 to enter the cell and then release the active parent drug in the target cell In this way, the concentration of LAT1 is many times higher than that of the mother drug alone This is very important, especially when the final target protein is in the cell The study was published in scientific reports in early September Photo source: https://cn.bing.com blood brain barrier (BBB) regulates the transfer of all substances from blood circulation to the brain Its main function is to protect the central nervous system (CNS) from harmful substances, while allowing the necessary nutrients, such as sugar, water and oxygen, to enter Therefore, most of the drug compounds that are believed to play a role in the brain do not penetrate through the blood-brain barrier at a high enough level to effectively treat brain diseases However, the BBB expresses several transporters through which essential nutrients are transferred from the blood circulation to the brain The team, led by kristinina Huttunen, an adjunct professor at the school of medicine at the University of eastern Finland, has been studying LAT1 for a long time They also demonstrated that LAT1 can be used effectively for brain targeting and enable drug delivery through the blood-brain barrier because it is highly expressed in the brain compared to any other healthy organ In this study, the research group studied the application of LAT1 in blood-brain targeted drug delivery after drug molecules pass through the blood-brain barrier This study is the first to confirm that functional LAT1 is not only expressed on the surface of neurons, but also in Sertoli cells, astrocytes and microglia In addition, it was found that prodrugs using several different compounds showed better cell uptake than their parent drugs The same results apply to astrocytes with Alzheimer's disease characteristics "We are also able to identify the structural needs of prodrugs to achieve targeting between different brain cell types in the future," said Dr Johanna Huttunen, the lead author of the study "Therefore, it is possible to obtain the drug concentration related to the pharmacological effect of the diseased brain by using the method of LAT1 prodrug, which is one of the main challenges to be overcome in the development of central nervous system drugs Associate professor Huttunen said that the best result is to develop more effective drugs to treat brain diseases Only when we consider the drug delivery in the brain as early as possible in the drug development stage, can we achieve the goal Now is the time for us to design new CNS drugs structurally Reference: Johanna Huttunen et al L-type amino acid transporter 1 (LAT1 / LAT1) - using prodrugs can improve the delivery of drugs into neurons, astrocytes and microglia, scientific reports (2019) Doi: 10.1038/s41598-019-49009-z