Correlation between beta-amyloid peptide production and human APP-induced neuronal death.
The production of amyloid peptide (Abeta) from its precursor (APP) plays a key role in Alzheimer's disease (AD). However, the link between Abeta production and neuronal death remains elusive. We studied the biological effects associated with human APP expression and metabolism in rat cortical neurons. Human APP expressed in neurons is processed to produce Abeta and soluble APP. Moreover, human APP expression triggers neuronal death. Pepstatin A, an inhibitor of aspartyl proteases that reduces Abeta production, protects neurons from APP-induced neurotoxicity. This suggests that Abeta production is likely to be the critical event in the neurodegenerative process of AD.
Université Catholique de Louvain, FARL/UCL 54 10, Av Hippocrate 54, B-1200 Brussels, Belgium.
Pascal
P
Kienlen-Campard
Jean-Noël
JN
Octave
D000256:Adenoviridae / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003470:Culture Media / Q000032:analysis; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D010436:Pepstatins / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011995:Recombination, Genetic
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003470:Culture Media; D009498:Neurotoxins; D010436:Pepstatins; D011480:Protease Inhibitors; C031375:pepstatin