Cholesterol-regulating complex of sirt1 and lxr and methods...

C - Chemistry – Metallurgy – 12 – Q

Patent

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C12Q 1/68 (2006.01) A61K 31/18 (2006.01) A61K 31/203 (2006.01) A61K 31/575 (2006.01) A61K 45/00 (2006.01) A61K 48/00 (2006.01) A61P 3/04 (2006.01) C07K 14/705 (2006.01) C12N 9/78 (2006.01) G01N 33/53 (2006.01) A61K 38/46 (2006.01) C07K 19/00 (2006.01)

Patent

CA 2654701

A cholesterol-regulating complex of SIRT1 and LXR and methods of use are disclosed. SIRTl forms a complex with LXR bound to an LXR element. Methods of forming the complex, identifying an agent that modulates formation of the complex, increasing the ratio of cholesterol bound to high density lipoprotein (HDL) to total cholesterol in the plasma of a mammal, promoting ABCA1 -mediated cholesterol efflux from a mammalian cell, treating a subject deemed to have a level of SIRT1 activity that is below normal, assessing whether a candidate substance modulates an LXR-dependent process, and assessing whether a candidate substance modulates an SIRTl -dependent effect of an LXR are disclosed.

La présente invention concerne un complexe de la protéine SIRT1 et du récepteur LXR régulant le cholestérol et des procédés d'utilisation. La SIRT1 forme un complexe avec le LXR par liaison avec un élément du LXR. L'invention concerne également des procédés permettant de former le complexe, l'identification d'un agent qui module la formation du complexe, l'augmentation du rapport du cholestérol lié à la lipoprotéine haute densité (HDL) au cholestérol total dans le plasma d'un mammifère, le processus favorisant l'efflux de cholestérol induit par ABCA1 d'une cellule mammalienne, le traitement d'un sujet supposé présenter un niveau d'activité de la SIRT1 au-dessous de la normale, l'évaluation de la modulation d'un processus dépendant du LXR par une substance candidate, et l'évaluation de la modulation de l'effet d'un LXR dépendant de la SIRT1 par une substance candidate.

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