Format

Send to

Choose Destination
Neuron. 1996 Jul;17(1):171-9.

Inhibition of amyloid beta-protein production in neural cells by the serine protease inhibitor AEBSF.

Author information

1
Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

Cerebral deposition of amyloid beta protein (A beta) is an early and critical feature of Alzheimer's disease. A beta production requires the proteolytic release of A beta from the beta-amyloid precursor protein (beta APP). Thus, inhibition of A beta release is a prime therapeutic goal. Here, we show that the broad spectrum, irreversible serine protease inhibitor, AEBSF, inhibits the constitutive production of A beta in five different human cell lines, both neural and nonneural. AEBSF also stabilizes full-length beta APP and enhances alpha-secretion, as shown by an increase in the proteolytic derivative, alpha-APPS. Further, we demonstrate that the inhibitory effect of AEBSF is specific for A beta proteins starting at Aspartate 1, suggesting that AEBSF directly inhibits beta-secretase, the Methionine-Aspartate (Met-Asp)-cleaving enzyme. These results indicate that specific inhibition of this A beta-generating protease is possible in living human neural cells and provide information about the characteristics of this as yet unidentified enzyme.

PMID:
8755488
DOI:
10.1016/s0896-6273(00)80290-1
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center