01 October 2015. Vol.6 No.5
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 Angiotensin II (AII) thought angiotensin converting enzyme (ACE), AII mediate their actions by angiotensin receptors AT1 and AT2Rs. AT1Rs activate
the nicotidamine adenine dinucleotide phosphate oxidase complex
(NADPH), which is the major source of ROS causing mitochondrial dysfunction and inflammatory response. The interaction AT1Rs with of D1 and D3Rs increases the DA response while D5Rs can regulate the AT1Rs by proteasome mechanisms. DA receptors are also related with immune response in T cells.