MOLECULAR HETEROGENEITY OF NEUROTRANSPORTERS - IMPLICATIONS FOR NEURODEGENERATION

Neurotransporters are high-affinity transport proteins located in the plasma membrane of both presynaptic nerve and glial cells that mediate the removal of neurotransmitters from the synaptic cleft or represent intracellular transport systems that concentrate neurotransmitters in synaptic vesicles. They comprise three subgroups, Na+/Cl-- or Na+/K+- dependent cell surface transporters and H+-dependent transporters asso ciated with synaptic vesicles. The new insights into neurotransporter diversity provide the means for novel approaches of studying neurotran smitter uptake processes at the molecular level, such as substrate tra nslocation and antagonist binding as well as regulation of gene expres sion, of intracellular trafficking, and of posttranslational modificat ion. Moreover, modeling neurotransporter-related disorders and therape utic strategies in genetically engineered animals are now feasible res earch strategies. Through an improved understanding of the modulation of neurotransporter function in the brain, it may be possible to ident ify the molecular factors underlying the etiopathogenesis and pathophy siology of neurodegenerative disorders. Due to their specificity for d istinct neuronal systems, neurotransporters and their genes are potent ial targets for novel therapeutic strategies.