PKCε increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice

Doo Sup Choi, Dan Wang, Gui Qui Yu, Guofen Zhu, Viktor N. Kharazia, J. Peter Paredes, Wesley S. Chang, Jason K. Deitchman, Lennart Mucke, Robert O. Messing

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Deposition of plaques containing amyloid β (Aβ) peptides is a neuropathological hallmark of Alzheimer's disease (AD). Here we demonstrate that neuronal overexpression of the ε isozyme of PKC decreases Aβ levels, plaque burden, and plaque-associated neuritic dystrophy and reactive astrocytosis in transgenic mice expressing familial AD-mutant forms of the human amyloid precursor protein (APP). Compared with APP singly transgenic mice, APP/PKCε doubly transgenic mice had decreased Aβ levels but showed no evidence for altered cleavage of APP. Instead, PKCε overexpression selectively increased the activity of endothelin-converting enzyme, which degrades Aβ. The activities of other Aβ-degrading enzymes, insulin degrading enzyme and neprilysin, were unchanged. These results indicate that increased neuronal PKCε activity can promote Aβ clearance and reduce AD neuropathology through increased endothelin-converting enzyme activity.

Original languageEnglish (US)
Pages (from-to)8215-8220
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number21
DOIs
StatePublished - May 23 2006

Keywords

  • Alzheimer's disease
  • Neurodegeneration
  • Phosphorylation
  • Proteolysis

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'PKCε increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice'. Together they form a unique fingerprint.

Cite this