Modulation of protein methylation and phosphoprotein phosphate

C - Chemistry – Metallurgy – 12 – Q

Patent

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Details

C12Q 1/42 (2006.01) A61K 38/46 (2006.01) A61K 45/00 (2006.01) C12Q 1/48 (2006.01)

Patent

CA 2477604

The invention relates to methylated proteins that control protein phosphorylation, particularly phosphoesterases, such as PP2A. It relates to screening methods for determining agents that affect methylation of these proteins and thus also modulate the level of phosphorylation of phosphoproteins. It relates as well to the agents and to compositions comprising the agents. In a particular aspect in this regard the invention relates to agents that alter PP2A methylation and that thereby affect phosphorylation of phosphoproteins that play an important role in health or disease, such as the tau protein which is implicated in the etiology of Alzheimer's Disease. The invention further relates to diagnostic methods based on protein methylation levels, to compositions comprising agents for affecting methylation of proteins and for controlling the phosphate complement of phosphoproteins. Additionally, the invention relates to methods for administering the agents and compositions to affect methylation of proteins physiologically and to modulate the phosphate complement of phosphoproteins. Examples in this regard include agents and compositions that affect physiological activity of PP2A and alter the phosphate complement of phosphoproteins that are altered in disease.

L'invention a trait à des protéines méthylées qui régulent la phosphorylation des protéines, en particulier aux phosphoestérases, telles que les PP2A. L'invention concerne des procédés de criblage permettant de mettre en évidence des agents qui influent sur la méthylation de ces protéines, et qui modulent donc également le niveau de phosphorylation des phosphoprotéines. L'invention se rapporte également auxdits agents, ainsi qu'à des compositions contenant lesdits agents. Dans un aspect donné, à cet égard, l'invention a trait à des agents qui modifient la méthylation des PP2A, et qui influent ainsi sur la phosphorylation des phosphoprotéines qui sont décisives pour l'état de santé ou de maladie d'un individu, telles que la protéine tau, qui intervient dans l'étiologie de la maladie d'Alzheimer. L'invention a également trait à des méthodes diagnostiques s'appuyant sur les niveaux de méthylation des protéines, à des compositions contenant des agents influant sur la méthylation des protéines et sur la régulation du complément phosphate des phosphoprotéines. De plus, l'invention concerne des méthodes d'administration des agents et de compositions influant physiologiquement sur la méthylation des protéines et modulant le complément phosphate des phosphoprotéines. Parmi les exemples pertinents, on trouve des agents et des compositions qui influent sur l'activité physiologique des PP2A et modifient le complément phosphate des phosphoprotéines qui subissent une altération en cas de maladie.

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