Serpins inhibit the toxicity of amyloid peptides.
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.
Schubert
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Cellular Neurobiology Laboratory, The Salk Institute, San Diego, CA 92186, USA.
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
D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D000514:alpha 1-Antichymotrypsin