Sirtuin 1 has been shown to deacetylate FOXO3 and FOXO4 and Sirtuin 1 has been involved in deacetylation of histone 3 (H3) and histone 4 (H4). Researchers have shown that epigenetically the binding of forkhead box O (FoxO) 3 to the promoter of PCSK9 recruits Sirt6 to deacetylate histone H3 suppressing PCSK9 expression. Sirtuin 1 is involved in the regulation of FOXO, H3 and H4 and may determine binding to the promoter of PCSK9 with interactions with Sirtuin 6 to determine PCSK9 expression. PCSK9 has been shown to be critical to plasma cholesterol levels and brain amyloidosis. Plasma PCSK9 inhibition in rodents regulates brain amyloidosis. In the plasma researchers now indicate that Sirtuin 1 binds PCSK9 and determine cholesterol and amyloid beta homeostasis. Sirtuin 1 inhibitors may increase plasma PCSK9 levels and determine elevated cholesterol levels and brain amyloidosis.
RELEVANT REFERENCES:
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H. Papotti, B. Adorni, M.P. Marchi, C. Zimetti, F. Ronda, N. Panighel, G.; Lupo, M.G. Vilella, A., Giuliani, D.; Ferri, N. et al. PCSK9 Affects Astrocyte Cholesterol Metabolism and Reduces Neuron Cholesterol Supplying In Vitro: Potential Implications in Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 23,12192.
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J. Miranda MX, van Tits LJ, Lohmann C, Arsiwala T, Winnik S, Tailleux A, Stein S, Gomes AP, Suri V, Ellis JL, Lutz TA, Hottiger MO, Sinclair DA, Auwerx J, Schoonjans K, Staels B, Lüscher TF, Matter CM. The Sirt1 activator SRT3025 provides atheroprotection in Apoe-/- mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression. Eur Heart J. 2015 Jan 1;36(1):51-9.
K. Melroy X Miranda, Tasneem Arsiwala, Slayman Obeid, Anne Tailleux Tailleux, Giovanni Pellegrini, Christian Matter, Bart Staels, Jose Manuel Fernandez-Real and Thomas F Luescher. Abstract 19426: Circulating Sirt1 Protects Against Atherosclerosis Through Its Modulation of Pcsk9 Activity. 29Mar 2018Circulation. 2016;134:A19426.
L. Single Gene Inactivation with Implications to Diabetes and Multiple Organ Dysfunction Syndrome. J Clin Epigenet. 2017; Vol. 3 No. 3:24.
M. Nutrition Therapy Regulates Caffeine Metabolism with Relevance to NAFLD and Induction of Type 3 Diabetes. J Diabetes Metab Disord. 2017; 4: 019.
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