Alpha 1-antichymotrypsin interaction with A beta (1-42) does not inhibit fibril formation but attenuates the peptide toxicity.
alpha 1-Antichymotrypsin (ACT) is intimately associated with senile plaques in the Alzheimer's diseased (AD) brain. It was reported that ACT can promote the polimerization of A beta (1-42) into amyloid filaments. It was suggested that neurotoxic amyloid deposits arise when beta-peptide is induced to form fibrils by ACT or other amyloid-promoting factors (pathological chaperones) expressed in AD brain. However, it was reported recently that ACT can inhibit fibrillization of A beta (1-40) and disaggregate pre-formed beta-amyloid fibrils of this synthetic A beta peptide. Our previous study [Aksenova et al., Neurosci. Lett., 411 (1996) 43-48] confirmed that ACT is able to inhibit A beta (1-40) aggregation into fibrils, but it was shown that at the same time ACT does not change the peptide cytotoxicity. In this report we have observed that interaction of ACT with A beta (1-42), unlike that for ACT-A beta (1-40) interaction, does not prevent the formation of insoluble A beta (1-42) aggregates, but completely blocks the peptide's toxicity in rat hippocampal cell cultures. These results are discussed in terms of the potential double role of peptide-protein interactions on A beta aggregation and neurotoxicity.
Department of Pharmacology, University of Kentucky, Lexington 40536, USA. myakse 1@ukcc.eku.edu
M Y
MY
Aksenov
M V
MV
Aksenova
J M
JM
Carney
D A
DA
Butterfield
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D004396:Coloring Agents; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D009454:Neurofibrils / Q000187:drug effects* / Q000648:ultrastructure; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D000514:alpha 1-Antichymotrypsin / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D009498:Neurotoxins; D010446:Peptide Fragments; D015842:Serine Proteinase Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D000514:alpha 1-Antichymotrypsin; C075222:amyloid beta-protein (1-42); C022616:thiazolyl blue