Recent studies have shown that a peptide produced from thyroptropin-releasing hormone (TRH) in the hypothalamus called cyclo (His-Pro) (CHP) can provide neuroprotective effects against a number of toxicants including Paraquat, rotenone, glutamate and B-amyloid. The author determined that these effects are generated through the activation of Nrf2 and that the protective effects against Paraquat also involve HO-1. Knock-down of Nrf2 abolished these protective effects. Generally, the studies show evidence that CHP improves glutathione synthesis and prevented depletion and reduces the generation of ROS from these toxicants. Specifically, he notes that CHP is protective against H2O2 mediated apoptotic cell death. (Minelli) Paraquat exposure has been implicated as a risk factor for Parkinson's disease and having adverse effects on dopamine systems.
Other studies have shown that dopamine transmission is regulated by H2O2 and that H2O2 generated from respiring mitochondria are the major source of H2O2 neuronal signals. As we have noted, toxicants and other factors can lead to mitochondrial dysfunction which has been implicated in a number of health conditions including those commonly known as environmental illness. In the striatum, H2O2 controls dopamine release and it has been found that H2O2 inhibits dopamine release and activity through the activation of KATP channels.
Notes:
CHP is a substrate for OCT2 according to Taubert. Jonker explains that knock-down of OCT1 and OCT2 in the kidney can lead to an inhibition of excretion and excessive concentration of tetraethylammonium in the blood. (Taubert, Jonker)
Kim Kramer
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