A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 31/70 (2006.01) A01K 67/00 (2006.01) G01N 33/00 (2006.01)
Patent
CA 2563926
In accordance with the present invention, it is demonstrated that selected mutations such as an Asp -> Ala (D664A) mutation in APP (which prevents cleavage at the caspase cleavage site) prevent both hippocampal synaptic loss and dentate gyral atrophy, even though such mutations do not interfere with the production of A~ or the formation of amyloid plaques in a transgenic model of Alzheimer's disease. Accordingly, in view of this finding, methods have been developed for the identification of agents which block cleavage at Asp664 of APP, including transgenic animals which are useful for such purpose, as well as methods for the use thereof for the treatment of neurodegenerative diseases.
Selon l'invention, il a été constaté que des mutations sélectionnées, telles qu'une mutation Asp .fwdarw. >Ala (D664A) dans APP (qui empêche le clivage au niveau du site de clivage de la caspase), empêchent la perte synaptique hippocampique et l'atrophie du corps godronné, même si ces mutations n'interfèrent pas avec la production d'A.beta. ou la formation de plaques amyloïdes dans un modèle transgénique de la maladie d'Alzheimer. Ainsi, au vu de cette découverte, on a mis au point des procédés d'identification d'agents qui bloquent le clivage au niveau d'Asp664 d'APP, dont des animaux transgéniques utiles à ces fins, ainsi que des méthodes d'utilisation de ceux-ci pour le traitement de maladies neurodégénératives.
Bredesen Dale E.
Galvan Veronica
Buck Institute
Gowling Lafleur Henderson Llp
LandOfFree
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