Modulation of Abeta levels by beta-secretase BACE2
AssigneeScios, Inc.
InventorsBarbara Cordell, Frauke Schimmoller, Yu-Wang Liu, Diana Hom Quon
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Abstract
The present invention is based on the findings that BACE2, a homolog of β-secretase BACE, is able to stimulate processing of APP in a non-amyloidogenic pathway, thereby suppressing the level of Aβ. Accordingly, the present invention provides methods and means for the identification and use of modulators of this unique activity of BACE2 to suppress Aβ production. The compounds identified using the methods and means provided herein may be used as potential candidates for the treatment of Alzheimer's disease and other neurological diseases.
Claims56
A method of modulating the enzymatic production of Aβ-amyloid peptide (Aβ) from Aβ-amyloid precursor protein (APP) or a fragment thereof, comprising contacting said APP or APP fragment with a BACE2 polypeptide or an agonist or antagonist thereof.
A method of inhibiting the formation of a β-amyloid peptide (Aβ) from β-amyloid precursor protein (APP) or a fragment thereof, comprising contacting said APP of APP fragment with a BACE2 polypeptide or an agonist thereof.
A method of inhibiting the release of a full-length β-amyloid (Aβ) polypeptide from β-amyloid precursor protein (APP) or a fragment thereof, comprising cleaving said APP or APP fragment by a BACE2 polypeptide or an agonist thereof at a site interfering with β-secretase processing of said APP or APP fragment.
A method for identifying a modulator of the enzymatic production of β-amyloid peptide (Aβ) from β-amyloid precursor protein (APP) or a fragment thereof, comprising contacting APP or an APP fragment and BACE2 with a candidate compound and monitoring the effect of the candidate compound on the production of Aβ.
A method for reducing the amount of Aβ-amyloid deposits in the central nervous system (CNS) of a mammal comprising administering to said mammal an effective amount of BACE2 or an agonist thereof.
A method for the treatment of Alzheimer's disease (AD), an AD-type pathology or cerebral amyloid angiopathy in a mammalian patient, comprising administering to said patient an effective amount of BACE2 or an agonist thereof.
Dependencies are inferred from the claim text.