| 摘要 |
A method for assaying hu-Asp1 a -secretase activity is claimed, comprising contacting hu-Asp1 protein with an amyloid precursor protein (APP) substrate containing an a -secretase cleavage site and measuring the cleavage of said substrate at said site. The hu-Asp1 amino acid sequence may comprise the sequence of SEQ ID NO:2 or preferably modified sequences are claimed lacking the amino terminal domain, transmembrane domain or cytoplasmic domain. Methods of identifying modulators of hu-Asp1 a -secretase activity as candidate Alzheimer's disease modulators and their use in therapeutic compositions are also claimed. Preferably the APP substrate contains the a -secretase cleavage site LVFFAEDF or KLVFFAED. Alternatively claimed is a hu-Asp1 substrate peptide comprising 50 or fewer amino acids including the cleavage site GLALALEP and methods of assaying hu-Asp1 proteolytic cleavage. The Hu-Asp2 b -secretase gene, polypeptide and assay for b -secretase activity is also described. |
