Compositions and methods for modulating nicotinic/nmda...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 14/705 (2006.01) A61K 38/16 (2006.01) A61K 38/17 (2006.01) A61K 39/395 (2006.01) A61P 25/34 (2006.01) C07K 7/06 (2006.01) C12N 15/12 (2006.01) C07K 16/28 (2006.01) C07K 19/00 (2006.01)

Patent

CA 2727141

The present invention provides a method for modulating nicotinic/NMDA receptor function in a mammal in need of such treatment comprising administering a therapeuti-cally effective amount of an agent that disrupts heterodimer-ization of .alpha.7 neuronal nicotinic acetylcholine receptors and N--methyl-D-asparate glutamate receptor. A polypeptide and frag-ments thereof comprising an amino acid sequence selected from the second intracellular loop of the .alpha.7 nAchR and car-boxyl tail of the N-methyl-D-aspartate receptor are also pro-vided, which are able to inhibit the heterodimerization. Also disclosed are nucleotide sequences encoding the polypeptides, and methods of inhibiting the heterodimerization of .alpha.7 nAchR and NMDAR using the polypeptides and nucleic acids.

La présente invention concerne un procédé de modulation de la fonction du récepteur nicotinique/NMDA chez un mammifère qui a besoin d'un tel traitement comprenant l'administration d'une quantité thérapeutiquement efficace d'un agent qui interrompt l'hétérodimérisation des récepteurs de l'acétylcholine nicotinique neuronale a7 et du récepteur du N-méthyl-D-asparate glutamate. L'invention concerne également un polypeptide et des fragments de celui-ci comprenant une séquence d'acides aminés choisis parmi la seconde boucle intracellulaire du a7 nAchR et l'extrémité carboxyle du récepteur N-méthyl-D-asparate, qui sont capables d'inhiber l'hétérodimérisation. L'invention concerne également des séquences nucléotidiques codant pour les polypeptides, et des procédés d'inhibition de l'hétérodimérisation des a7 nAchR et NMDAR en utilisant les polypeptides et les acides nucléiques.

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