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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. Nature. 2018 Apr 5;556(7699):113-117. doi: 10.1038/nature25986. Epub 2018 Mar 28. Nature. 2018. PMID: 29590092 Free PMC article.
Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction.
Meakin PJ, Coull BM, Tuharska Z, McCaffery C, Akoumianakis I, Antoniades C, Brown J, Griffin KJ, Platt F, Ozber CH, Yuldasheva NY, Makava N, Skromna A, Prescott A, McNeilly AD, Siddiqui M, Palmer CN, Khan F, Ashford ML. Meakin PJ, et al. J Clin Invest. 2020 Aug 3;130(8):4104-4117. doi: 10.1172/JCI122237. J Clin Invest. 2020. PMID: 32407295 Free PMC article.
The BACE1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling.
Botteri G, Salvadó L, Gumà A, Lee Hamilton D, Meakin PJ, Montagut G, Ashford MLJ, Ceperuelo-Mallafré V, Fernández-Veledo S, Vendrell J, Calderón-Dominguez M, Serra D, Herrero L, Pizarro J, Barroso E, Palomer X, Vázquez-Carrera M. Botteri G, et al. Metabolism. 2018 Aug;85:59-75. doi: 10.1016/j.metabol.2018.03.005. Epub 2018 Mar 9. Metabolism. 2018. PMID: 29526536 Free article.
Small vessels, dementia and chronic diseases - molecular mechanisms and pathophysiology.
Horsburgh K, Wardlaw JM, van Agtmael T, Allan SM, Ashford MLJ, Bath PM, Brown R, Berwick J, Cader MZ, Carare RO, Davis JB, Duncombe J, Farr TD, Fowler JH, Goense J, Granata A, Hall CN, Hainsworth AH, Harvey A, Hawkes CA, Joutel A, Kalaria RN, Kehoe PG, Lawrence CB, Lockhart A, Love S, Macleod MR, Macrae IM, Markus HS, McCabe C, McColl BW, Meakin PJ, Miller A, Nedergaard M, O'Sullivan M, Quinn TJ, Rajani R, Saksida LM, Smith C, Smith KJ, Touyz RM, Trueman RC, Wang T, Williams A, Williams SCR, Work LM. Horsburgh K, et al. Clin Sci (Lond). 2018 Apr 30;132(8):851-868. doi: 10.1042/CS20171620. Print 2018 Apr 30. Clin Sci (Lond). 2018. PMID: 29712883 Free PMC article.