Methods and compositions for monitoring cellular processing of beta-amyloid precursor protein
First Claim
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1. An in vitro method of screening compounds to identify β
- -amyloid production inhibitors, said method comprising;
(a) culturing cells Under conditions which result in a secretion of a soluble fragment of β
-amyloid precursor protein (β
APP), wherein an amino acid sequence of said soluble β
APP fragment extends substantially from the amino-terminus of β
APP to the amino-terminus of β
-amyloid peptide;
(b) exposing the cultured cells to a test compound; and
(c) detecting an amount of said soluble β
APP fragment;
whereby a decrease in the amount of said soluble β
APP fragment as compared to the amount of soluble β
APP fragment from cells not exposed to the compound indicates that the compound is a β
-amyloid production inhibitor.
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Abstract
The present invention provides methods for identifying beta amyloid production inhibitors, wherein cells are cultured under conditions which result in secretion of a soluble fragment of beta amyloid precursor protein. The amino acid sequence of the fragment extends from the amino terminus of beta APP to the amino terminus of the beta amyloid peptide. The cultured cells are exposed to test compounds which cause a change in the secreted amount of the soluble fragment of beta APP which is determined.
181 Citations
7 Claims
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1. An in vitro method of screening compounds to identify β
- -amyloid production inhibitors, said method comprising;
(a) culturing cells Under conditions which result in a secretion of a soluble fragment of β
-amyloid precursor protein (β
APP), wherein an amino acid sequence of said soluble β
APP fragment extends substantially from the amino-terminus of β
APP to the amino-terminus of β
-amyloid peptide;(b) exposing the cultured cells to a test compound; and (c) detecting an amount of said soluble β
APP fragment;
whereby a decrease in the amount of said soluble β
APP fragment as compared to the amount of soluble β
APP fragment from cells not exposed to the compound indicates that the compound is a β
-amyloid production inhibitor. - View Dependent Claims (2, 3, 4, 5, 6, 7)
- -amyloid production inhibitors, said method comprising;
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Current AssigneeElan Pharmaceuticals Incorporated (Perrigo Company PLC)
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Original AssigneeEli Lilly and Company, Athena Neurosciences Incorporated (Perrigo Company PLC)
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InventorsSchenk, Dale B., Seubert, Peter A., Fritz, Lawrence C.
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Primary Examiner(s)Gitomer, Ralph
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Application NumberUS08/440,261Time in Patent Office655 DaysField of Search435/7.4, 435/23, 435/24, 435/29, 435/41, 435/69.2, 435/184, 424/9.2US Class Current435/29CPC Class CodesC07K 14/4711 Alzheimer's disease; Amyloi...C07K 16/18 against material from anima...G01N 2333/4709 Amyloid plaque core proteinG01N 2800/2821 AlzheimerG01N 33/5008 for testing or evaluating t...G01N 33/6896 Neurological disorders, e.g...
