Methods, compositions and compound assays for inhibiting...

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G01N 33/68 (2006.01) G01N 33/566 (2006.01)

Patent

CA 2605574

A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a GPCR polypeptide, (eg. GPR3, GPR6, GPR12) or fragment thereof, and measuring a compound-GPCR property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including second messenger and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of GPCR expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimers Disease.

L'invention concerne une méthode destinée à identifier des composés inhibant la synthèse d'une protéine précurseur bêta-amyloïde dans les cellules, et consistant à mettre un composé d'essai en contact avec un polypeptide GPCR, ou un fragment correspondant, et à mesurer une propriété composé-GPCR associée à la production d'un peptide bêta-amyloïde. Des analyses cellulaires de cette méthode permettent de mesurer des indicateurs comprenant les taux de second messager et/ou de peptide bêta-amyloïde. Ces méthodes thérapeutiques, de même que les compositions pharmaceutiques renfermant des doses inhibant la synthèse de précurseur bêta-amyloïde d'inhibiteurs de l'expression de GPCR, sont utiles pour traiter des affections caractérisées par une déficience cognitive, telles que la maladie d'Alzheimer.

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