Format

Send to

Choose Destination
Neuron. 1995 Mar;14(3):651-9.

Inhibition of beta-amyloid formation identifies proteolytic precursors and subcellular site of catabolism.

Author information

1
Scios Nova Incorporated, Mountain View, California 94043.

Abstract

Cerebral deposition of beta-amyloid protein is a pathological feature central to Alzheimer's disease. Production of beta-amyloid by proteolytic processing of the beta-amyloid precursor protein (beta APP) is a critical initial step in beta-amyloidogenesis. We use an inhibitor of beta APP processing to block beta-amyloid peptide formation. Application of the inhibitor to cultured cells results in an accumulation of proteolytic intermediates of beta APP, enabling a precursor-product relationship between beta APP carboxy-terminal fragments and beta-amyloid peptides to be demonstrated directly. In the presence of inhibitor, these amyloidogenic carboxy-terminal fragments can be degraded to nonamyloidogenic products. The catabolism of beta APP carboxy-terminal intermediates and the formation of beta-amyloid peptides are likely to involve an early endosomal compartment as the subcellular site of processing.

PMID:
7695912
DOI:
10.1016/0896-6273(95)90322-4
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center