Model for alzheimer's disease and other neurodegenerative...

G - Physics – 01 – N

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G01N 33/68 (2006.01)

Patent

CA 2417744

The present invention provides a model for studying the development of, and/or pathologies associated with neurodegenerative diseases, and agents that can alter such development and/or pathologies. The model of the invention is especially useful as an Alzheimer's disease model. The model of the invention provides brain cells and a method for increasing neurodegenerative disease characteristics in such cells, especially, introductino of neurofibrillary tangles and/or phosphorylated tau and/or tau fragments and/or the production and/or release of cytokines and/or microglia reactions and/or activations and/or inflammation and/or conversion of p35 to p25 and/or the levels and activities of protein kinases by selectively increasing the concentration of cathepsin D to an effective level, and/or by lowering the concentration of cholesterol in such cells. The model also provides a method of reversing such effects, by inhibiting cysteine protease and mitogen-activated kinase activity, and especially, by inhibiting calpain, and/or MAP kinase.

La présente invention porte sur un modèle permettant d'étudier le développement des maladies neurodégénératives et/ou des pathologies associées à ces maladies, et sur des agents pouvant modifier ce développement et/ou ces pathologies. Le modèle de cette invention est notamment utile comme modèle de la maladie d'Alzheimer. Le modèle de cette invention concerne les cellules cérébrales et un procédé visant à accroître les caractéristiques des maladies neurodégénératives dans ces cellules, notamment, l'induction de la dégénérescence neurofibrillaire et/ou tau phosphorylé et/ou des fragments tau et/ou la production et/ou la libération des cytokines et/ou des réactions des microglies et/ou des activations et/ou l'inflammation et/ou la conversion de p35 en p25 et/ou les taux et les activités des protéines kinases en augmentant sélectivement la concentration de la cathepsine D à un taux efficace, et/ou en réduisant la concentration du cholestérol dans ces cellules. Le modèle concerne également un procédé d'inversion de ces effets en inhibant la cystéine protéase et l'activité de la kinase activée par un mitogène, et notamment, en inhibant calpain, et/ou MAP kinase.

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