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Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1.
Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, Jedrychowski MP, Costa ASH, Higgins M, Hams E, Szpyt J, Runtsch MC, King MS, McGouran JF, Fischer R, Kessler BM, McGettrick AF, Hughes MM, Carroll RG, Booty LM, Knatko EV, Meakin PJ, Ashford MLJ, Modis LK, Brunori G, Sévin DC, Fallon PG, Caldwell ST, Kunji ERS, Chouchani ET, Frezza C, Dinkova-Kostova AT, Hartley RC, Murphy MP, O'Neill LA. Mills EL, et al. Among authors: meakin pj. Nature. 2018 Apr 5;556(7699):113-117. doi: 10.1038/nature25986. Epub 2018 Mar 28. Nature. 2018. PMID: 29590092 Free PMC article.
Neuronal development is promoted by weakened intrinsic antioxidant defences due to epigenetic repression of Nrf2.
Bell KF, Al-Mubarak B, Martel MA, McKay S, Wheelan N, Hasel P, Márkus NM, Baxter P, Deighton RF, Serio A, Bilican B, Chowdhry S, Meakin PJ, Ashford ML, Wyllie DJ, Scannevin RH, Chandran S, Hayes JD, Hardingham GE. Bell KF, et al. Among authors: meakin pj. Nat Commun. 2015 May 13;6:7066. doi: 10.1038/ncomms8066. Nat Commun. 2015. PMID: 25967870 Free PMC article.
Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis.
Chowdhry S, Nazmy MH, Meakin PJ, Dinkova-Kostova AT, Walsh SV, Tsujita T, Dillon JF, Ashford ML, Hayes JD. Chowdhry S, et al. Among authors: meakin pj. Free Radic Biol Med. 2010 Jan 15;48(2):357-71. doi: 10.1016/j.freeradbiomed.2009.11.007. Epub 2009 Nov 13. Free Radic Biol Med. 2010. PMID: 19914374
Susceptibility of Nrf2-null mice to steatohepatitis and cirrhosis upon consumption of a high-fat diet is associated with oxidative stress, perturbation of the unfolded protein response, and disturbance in the expression of metabolic enzymes but not with insulin resistance.
Meakin PJ, Chowdhry S, Sharma RS, Ashford FB, Walsh SV, McCrimmon RJ, Dinkova-Kostova AT, Dillon JF, Hayes JD, Ashford ML. Meakin PJ, et al. Mol Cell Biol. 2014 Sep;34(17):3305-20. doi: 10.1128/MCB.00677-14. Epub 2014 Jun 23. Mol Cell Biol. 2014. PMID: 24958099 Free PMC article.
Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome.
Rzepecka J, Pineda MA, Al-Riyami L, Rodgers DT, Huggan JK, Lumb FE, Khalaf AI, Meakin PJ, Corbet M, Ashford ML, Suckling CJ, Harnett MM, Harnett W. Rzepecka J, et al. Among authors: meakin pj. J Autoimmun. 2015 Jun;60:59-73. doi: 10.1016/j.jaut.2015.04.005. Epub 2015 May 11. J Autoimmun. 2015. PMID: 25975491 Free PMC article.
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