Oxidative Stress and Decreased Mitochondrial Superoxide Dismutase 2 and Peroxiredoxins 1 and 4 Based Mechanism of Concurrent Activation of AMPK and mTOR in Alzheimer's Disease

Current Alzheimer Research
Shohreh Majd, John Power

Abstract

Emerging evidence supports the hypothesis that metabolism dysfunction is involved in pathogenesis of Alzheimer's disease (AD). One aspect of metabolic dysfunction includes dysregulation of adenosine monophosphate kinase protein kinase (AMPK) and mammalian target of rapamycin (mTOR) metabolic axis, which is extensively present in some of the leading causes of AD such as cerebrovascular diseases, type 2 diabetes and brain ischaemic events. While the molecular basis underlying this metabolic dysregulation remains a significant challenge, mitochondrial dysfunction due to aging appears to be an essential factor to activate AMPK/mTOR signaling pathway, leading to abnormal neuronal energy metabolism and AD pathology. Using immunofluorescent imaging by Lecia confocal microscopy, we analyzed the activation of AMPK/mTOR. Concurrently, the level of mitochondrial antioxidant enzymes of superoxide dismutase 2 (SOD2) and peroxiredoxin 1 and 4 (p1 and p4) along with protein and DANA oxidation were examined to in postmortem brains of AD (n= 8) and normal (n= 7) subjects to evaluate the metabolism dysfunction role in AD pathology. In spite of AMPK inhibitory control on mTOR, concurrent phosphorylation of AMPK and mTOR (p-AMPK and p-mTOR) was ob...Continue Reading

Citations

Oct 31, 2018·Frontiers in Neuroscience·Shreedarshanee DeviRanjana Arya
Nov 27, 2018·Journal of Alzheimer's Disease : JAD·Sabrina StrobelCamelia-Maria Monoranu
Aug 12, 2018·International Journal of Molecular Sciences·Laura GiustiSilvana Hrelia
May 28, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xianying FangFuliang Cao
Mar 19, 2019·Frontiers in Neuroscience·Shohreh MajdZohreh Majd
Aug 23, 2020·International Journal of Molecular Sciences·Marianna CrispinoMaria Pina Mollica
Aug 13, 2020·International Journal of Molecular Sciences·Clara RuzSara Bandres-Ciga
Dec 4, 2020·Antioxidants·Monika Szeliga
Aug 14, 2021·Cell Stress & Chaperones·Elham RazaniDavood Bashash
Sep 11, 2021·Free Radical Biology & Medicine·Owen Davis SandersJayalekshmi Archa Rajagopal
May 28, 2021·CNS & Neurological Disorders Drug Targets·Marjan NikbakhtzadehGhorbangol Ashabi

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