Beta-amyloid increases cathepsin D levels in hippocampus.
A previous study established that beta-amyloid(1-42) is sequestered and retained intact for extended periods by select populations of neurons in cultured hippocampal slices. The present experiment tested if this effect is accompanied by increases in cathepsin D, a characteristic feature of lysosomal dysfunction and one that has been implicated in key aspects of brain aging in humans. Slices incubated with beta-amyloid(1-42) (15-30 microM) for 6 days had 56% greater concentrations of cathepsin D than controls. Scrambled peptides had no effect. The amyloid-induced increase was additive with that produced by submaximal concentrations of an inhibitor of cathepsins B and L but occluded that caused by chloroquine. This pattern of results (1) indicates that the uptake of amyloid results in lysosomal dysfunction and (2) suggests that perturbations of intralysosomal pH may contribute to this effect.
Center for the Neurobiology of Learning and Memory, University of California, Irvine, USA.
K B
KB
Hoffman
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Bi
J T
JT
Pham
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Lynch
D000544:Alzheimer Disease / Q000201:enzymology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D002402:Cathepsin D / Q000502:physiology*; D046508:Culture Techniques; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology* / Q000503:physiopathology*; D006801:Humans; D008247:Lysosomes / Q000473:pathology; D010446:Peptide Fragments / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D002402:Cathepsin D