Methods for identifying and using amyloid-inhibitory compounds

Details Methods for identifying and using amyloid-inhibitory compounds Methods for identifying and using amyloid-inhibitory compounds

G - Physics

01

N

G01N 33/68 (2006.01)

Patent

CA 2390161

The present invention relates to identification of agents that play a role in regulating brain amyloid-.beta. (A.beta.) levels in vivo. The invention provides compounds and methods of using such compounds to treat amyloidogenic conditions. It also provides a useful animal model for screening for and evaluating candidate amyloid inhibiting or therapeutic compounds. In particular, ovariectomy (ovx) and estrogen replacement were found to affect brain A.beta. levels in guinea pigs. Long-term ovx of guinea pigs resulted in increased levels of total brain A.beta., as compared to intact animals, and the A.beta.42/A.beta.40 ratio was also elevated. Treatment of ovx guinea pigs with .beta.17-estradiol for ten days partially reversed the ovx-associated increase in brain A.beta. levels.

L'invention concerne l'identification d'agents jouant un rôle dans la régulation des niveaux (A.beta.) de l'amyloïde-.beta. du cerveau in vivo. Cette invention concerne également des composés et des procédés utilisant ces composés afin de traiter des conditions amyloïdogéniques. L'invention concerne encore un modèle servant au dépistage et à l'évaluation de composés candidats thérapeutiques ou inhibant l'amyloïde. En particulier, l'ovariectomie (ovx) et le remplacement d'oestrogène ont montré qu'ils affectaient les niveaux A.beta. du cerveau chez les cobayes. L'ovx de cobayes provoque à long terme des augmentations des niveaux A.beta. du cerveau total par rapport à d'autres animaux intacts et le taux de A.beta.42/A.beta.40 est également plus élevé. Le traitement de l'ovx des cobayes par oestradiol-.beta.17 pendant dix jours inverse partiellement l'augmentation des niveaux A.beta. du cerveau associé à l'ovx.

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