Dopamine compartmentalization, selective dopaminergic vulnerabilities in Parkinson's disease and therapeutic opportunities

• Published in: Annals of clinical and translational neurology Vol. 6; no. 2; pp. 406 - 415
• Main Author: Uhl, George R.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.02.2019; John Wiley and Sons Inc
• Subjects: Corpus Striatum - metabolism; Dopamine; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - metabolism; Dopaminergic Neurons - metabolism; Humans; Parkinson Disease - metabolism; Parkinson Disease - therapy; Parkinson's disease; Review; Vesicular Monoamine Transport Proteins - metabolism; New Mexico; United States > US
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.707

Progressive depletion of selected dopamine neurons is central to much Parkinson's disease (PD) disability. Although symptomatic treatments can ameliorate the disabilities that this neuronal depletion causes, no current strategy is documented to slow these losses. There is substantial evidence that dopamine in intracytoplasmic/extravesicular neuronal compartments can be toxic. Here, I review evidence that supports roles for dopamine compartmentalization, mediated largely by serial actions of plasma membrane SLC6A3/DAT and vesicular SLC18A2/VMAT2 transporters, in the selective patterns of dopamine neuronal loss found in PD brains. This compartmentalization hypothesis for the dopamine cell type specificity of PD lesions nominates available drugs for amelioration of damage arising from miscompartmentalized dopamine and raises cautions in using other drugs.