Dopamine Receptors and Neurodegeneration Claudia Rangel-Barajas 1, 2 ; Israel Coronel 3 ; Benjam#cod#x 000 ED; n Flor#cod#x 000 E 1; n 4 ; 1 Department of Psychological and Brain Sciences Program in Neurosciences, Indiana University Bloomington, IN 47405, USA ; 2 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. ; 3 Health Sciences Faculty, Anahuac University, Mexico Norte, State of Mexico, Mexico. ; 4 Department of Physiology, Biophysics and Neurosciences CINVESTAV-IPN, Mexico. ; Figure 3. Oxidative stress and Neurotoxicity. A. Shows the neurotoxic mechanisms of DA and neurotoxins used to mimic PD in the dopaminergic neuron. DA and the neurotoxins 6 -hydroxydopmine 6 -OHDA and 1 -methyl-4 -phenyl-1, 2, 3, 6 -tetrahydropyridine MPTP, cause reactive species of oxygen ROS affecting the mitochondrial function and lipoperoxidation and cytoskeletal disorganization, which leads energy crisis and neuronal death. MPTP is first incorporated into the glial cells and metabolized to MPP + , this metabolite can cross the membrane through the DA transporter DAT to reach intracellular compartments in DAergic neuron, while 6 -OHDA can directly cross through DAT. B. Neurotoxicity by renin-angiotensin system RAS activation and DA receptors. In RAS, angiotensinogen is converted to Angiotensin I AI by renin, AI is converted into Aging and Disease, null, 6(5), 349 -368. Doi: 10. 14336/AD. 2015. 0330 mediate their actions by angiotensin receptors AT 1 and AT 2 Rs. AT 1 Rs activate the nicotidamine Angiotensin II AII thought angiotensin converting enzyme ACE, AII adenine dinucleotide phosphate oxidase complex NADPH, which is the major source of ROS causing mitochondrial dysfunction and inflammatory response. The interaction AT 1 Rs with of D 1 and D 3 Rs increases the DA response while D 5 Rs can regulate the AT 1 Rs by proteasome mechanisms. DA receptors are also related with immune response in T cells.
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