The binding of Sirtuin 1 to PCSK9 is important to reduce PCSK9 levels and reduce low density lipoprotein cholesterol. In man low Sirtuin 1 has been shown to be associated with cardiovascular disease, NAFLD and neurodegenerative diseases. The role of increased PCSK9 levels with low Sirtuin 1 levels may determine the peripheral sink amyloid beta clearance with accelerated amyloidosis and defective treatment of Alzheimer’s disease (AD).
RELEVANT REFERENCES:
A. Mazura, A.D., Ohler, A., Storck, S.E. et al. PCSK9 acts as a key regulator of Aβ clearance across the blood–brain barrier. Cell. Mol. Life Sci. 79, 212 (2022).
B. Appetite Regulation and the Peripheral Sink Amyloid beta Clearance Pathway in Diabetes and Alzheimer’s Disease. Top 10 Commentaries in Alzheimer’s Disease (e-book). 2019;2:1-11.
C. 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;36(1):51-9.
D. Toulassi I A, Al Saedi U A, Gutlapalli S, et al. (January 16, 2021) A Paradigm Shift in the Management of Atherosclerosis: Protective Role of Sirtuins in Atherosclerosis. Cureus. 2021; 13(1): e12735.
E. Melroy X Miranda, Tasneem Arsiwala, Slayman Obeid, Anne Tailleux Tailleux, Giovanni Pellegrini, Christian Matter, Bart Staels, Jose Manuel Fernandez-Real and Thomas F Luescher. Circulating Sirt1 Protects Against Atherosclerosis Through Its Modulation of Pcsk9 Activity. Circulation. 2016;134:A19426. Atherosclerosis, Vascular Biology and Development Session Title: Best of Basic Science Posters Abstract 19426.
F. O’Connell EM and Lohoff FW. (2020) Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in the Brain and Relevance for Neuropsychiatric Disorders. Front. Neurosci. 14:609.
G. Anti-Aging Genes Improve Appetite Regulation and Reverse Cell Senescence and Apoptosis in Global Populations. Advances in Aging Research, 2016, 5, 9-26
H. Single Gene Inactivation with Implications to Diabetes and Multiple Organ Dysfunction Syndrome. J Clin Epigenet. 2017;Vol. 3 No. 3:24.
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