title: Serpins inhibit the toxicity of amyloid peptides.
abstract: The amyloid plaque in Alzheimer's disease (AD) contains numerous proteins, some of which may be relevant to the pathogenesis of the disease. The serine protease inhibitor alpha1-antichymotrypsin is specifically localized in AD plaques. It is shown here that alpha1-antichymotrypsin and several other serine protease inhibitors (serpins) inhibit the toxicity of amyloid peptides on primary cortical nerve cell cultures as well as a clonal cell line. This inhibition of toxicity is not mediated via the serpin enzyme complex receptor, the transferrin receptor, or by interference with the polymerization of amyloid fibrils. Since a variety of synthetic serine protease inhibitors mimic the effects of serpins on amyloid toxicity, it is likely that the antiprotease activities of serpins are responsible for their biological effects.
authors.affiliation: Cellular Neurobiology Laboratory, The Salk Institute, San Diego, CA 92186, USA.
authors.forename: D
authors.initials: D
authors.lastname: Schubert
mesh_terms: D007516:Adenoma, Islet Cell; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002999:Clone Cells; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D010190:Pancreatic Neoplasms; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D015843:Serpins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000514:alpha 1-Antichymotrypsin / Q000494:pharmacology
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D000514:alpha 1-Antichymotrypsin