Amino Acid Transport Systems A and N as Targets for Synthetic Drug Design in the Treatment of Neurodegenerative Disorders

Abstract

L-glutamine, is the most abundant amino acid in the body. In the glutamatergic cycle, this amino acid is converted to and from the important neurotransmitter glutamate, which can be harmful when present in large amounts. In this study analogues of L-glutamine (designed to inhibit action of amino acid transport systems N and A) were screened on the rat isoform 1 of system N transport protein (rSNl) and the human isoform 2 of system A (hATA2) for effectiveness. These drugs were designed with the hopes of drug development in the treatment of neurodegenerative disorders. This experiment was carried out using radiolabeled uptake assays and electrophysiological recordings, both on Xenopus laevis oocytes expressing the transporter on its surface. Electrophysiology was investigated as a potential more efficient screening method, and the data was compared to that generated in radiolabeled glutamine uptake assays. Two potential inhibitors of rSNl were discovered as well as four potential inhibitors of hATA2. Although further studies are necessary to conclusively validate the results generated in this study, the pharmacology of two amino acid transport systems (N and A) has been further elucidated.