Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.
The molecular mechanism responsible for the neurodegeneration in Alzheimer disease is not known; however, accumulating evidence suggests that beta-amyloid peptide (A beta P) contributes to this degeneration. We now report that synthetic A beta Ps trigger the degeneration of cultured neurons through activation of an apoptotic pathway. Neurons treated with A beta Ps exhibit morphological and biochemical characteristics of apoptosis, including membrane blebbing, compaction of nuclear chromatin, and internucleosomal DNA fragmentation. Aurintricarboxylic acid, an inhibitor of nucleases, prevents DNA fragmentation and delays cell death. Our in vitro results suggest that apoptosis may play a role in the neuronal loss associated with Alzheimer disease.
Loo
D T
DT
Irvine Research Unit in Brain Aging, University of California 92717.
Copani
A
A
Pike
C J
CJ
Whittemore
E R
ER
Walencewicz
A J
AJ
Cotman
C W
CW
D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004247:DNA / Q000187:drug effects / Q000302:isolation & purification; D004249:DNA Damage; D004622:Embryo, Mammalian; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D004247:DNA