The use of Seldi ProteinChip? Arrays to monitor production of Alzheimer's ?-amyloid in transfected cells

摘要: β-Amyloid (Aβ), a 39-43 residue peptide, is the principal component of senile plaques found in brains patients with Alzheimer's disease (AD). There are two main lines evidence that its deposition cause neurodegeneration. First, mutations three genes familial cases give rise to increased production longest, most toxic, form, Aβ 1-42. Second, aggregated toxic neuronal cells culture. Inhibitors proteases involved release from amyloid precursor protein are, therefore, major therapeutic interest. The best candidates for releasing both aspartyl proteases, which integrated into membranes endoplasmic reticulum and Golgi network. A sensitive assay using Ciphergen's Seldi™ system has been developed measure all variants culture supernatants, will be great value screening inhibitors these proteases. With this assay, it shown increasing intracellular cholesterol increases activities β-secretase, γ-secretase-42. Moreover, changing targeting glycoprotein (APP) yields α-secretase cleavage, amounts oxidized/nitrated forms Aβ. Copyright © 2000 European Peptide Society John Wiley & Sons, Ltd.