Affordable Access

Publisher Website

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

Authors
Journal
Neuron
0896-6273
Publisher
Elsevier
Publication Date
Volume
14
Issue
3
Identifiers
DOI: 10.1016/0896-6273(95)90322-4
Disciplines
  • Biology
  • Medicine

Abstract

Abstract Cerebral deposition of β-amyloid protein is a pathological feature central to Alzheimer's disease. Production of β-amyloid by proteolytic processing of the β-amyloid precursor protein (βAPP) is a critical initial step in β-amyloidogenesis. We use an inhibitor of βAPP processing to block β-amyloid peptide formation. Application of the inhibitor to cultured cells results in an accumulation of proteolytic intermediates of βAPP, enabling a precursor-product relationship between βAPP carboxy-terminal fragments and β-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 βAPP carboxy-terminal intermediates and the formation of β-amyloid peptides are likely to involve an early endosomal compartment as the subcellular site of processing.

There are no comments yet on this publication. Be the first to share your thoughts.