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A High-Throughput Screen to Identify Inhibitors of Amyloid ß-Protein Precursor ProcessingCenter for Neurologic Diseases and Laboratory for Drug Discovery in Neurodegeneration, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
Laboratory for Drug Discovery in Neurodegeneration, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
Laboratory for Drug Discovery in Neurodegeneration, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
Laboratory for Drug Discovery in Neurodegeneration, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
Cerebral accumulation of the amyloid ß-peptide (Aß) is believed to play a key role in the pathogenesis of Alzheimer’s disease (AD). Because Aß is produced from the proteolysis of amyloid ß-protein precursor (APP) by ß-and
Key Words: Alzheimer’s disease • high-throughput screening • luciferase • amyloid •
Journal of Biomolecular Screening, Vol. 10, No. 1,
1-12 (2005) This article has been cited by other articles:
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-secretases, these enzymes are considered important drug targets for AD. The authors have developed a luciferase-based reporter system that can identify new molecules that inhibit APP processing in a high-throughput manner. Such molecules can help in understanding the biology of APP and APP processing and in developing new drug prototypes for AD. In this system, APP is fused on its C-terminus with Gal4-VP16, a chimeric yeast-viral transcription activator, and luciferase is under control of the yeast Gal4 promoter. Compounds that modulate the luciferase signal may affect the secretases directly, interact with modifiers of these proteases, or interact with APP directly. The authors successfully interfaced this assay with a high-throughput screen, testing ~60,000 compounds with diverse chemical structures. In principle, this sensitive, specific, and quantitative assay may be useful for identifying both inhibitors and stimulators of APP processing.(Journal of Biomolecular Screening 2005:1-12) 
