Resting state fMRI based target selection for individualized rTMS: Stimulation over the left parietal cortex enhances memory in patients with Alzheimer's disease
Year: 2019
Type: article
Abstract: exerts deleterious effects in the brain via various mechanism.One mechanism might be through increasing oxidative stress.Nuclear factor (erythroid-derived 2) like 2 (Nrf2), an endogenous antioxidant defence pathway has been found to play significant role in combating oxidative stress.Aim: The present study was designed to explore the effect of over activation of kynurenine pathway leading to increased QA on Keap1/Nrf2/ARE pathway in olfactory bulbectomized mice.Observations: QA inhibition showed significant reversal in depressive-like behaviour, restored decreased Nrf2 mRNA and protein levels and associated antioxidant levels (GCLC, NOQ1, HO-1, Catalase, SOD, GSH) in cortex and hippocampus of OBX-mice.QA inhibition increased PI3K/AKT mRNA expression decreased GSK3 mRNA expression in cortex and hippocampus in OBXmice.Outcomes of the in-vivo studies showed QA inhibition enhances Nrf2 activity by both Keap-1 dependent and Keap-1 independent pathway.Inhibition of QA significantly decreased inflammatory markers (IFN-␥, IL-6, TNF-␣ and NF-KB), kynurenine and increased serotonin, 5-hydroxyindolec acetic acid and tryptophan in hippocampus and cortex in OBX-mice.Using molecular docking studies we found that QA showed good binding affinity towards ubiquitin proteasome complex and PI3K protein involved in Keap1 dependent and Keap1 independent proteasome degradation of Nrf2 respectively.In-silico results are corroborated with in-vivo studies.Conclusion: QA might act as pro-oxidant through downregulating Nrf2/ARE pathway.
Source: IBRO Reports
Institutions: Sir Run Run Shaw Hospital, Zhejiang University
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,500
OpenAlex ID: W2973808295