References
Query Results -- Details
MGI Accession ID: MGI:3639629
J Number: J:110206
Other Accession IDs:
Title: PKCepsilon increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice.
Authors: Choi DS; Wang D; Yu GQ; Zhu G; Kharazia VN; Paredes JP; Chang WS; Deitchman JK; Mucke L; Messing RO
Journal: Proc Natl Acad Sci U S A
Volume: 103
Issue: 21
Date: 2006 May 23
Year: 2006
Pages: 8215-20
Review Status: Peer Reviewed
Abstract:
Deposition of plaques containing amyloid beta (Abeta) peptides is a neuropathological hallmark of Alzheimer's disease (AD). Here we demonstrate that neuronal overexpression of the epsilon isozyme of PKC decreases Abeta 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/PKCepsilon doubly transgenic mice had decreased Abeta levels but showed no evidence for altered cleavage of APP. Instead, PKCepsilon overexpression selectively increased the activity of endothelin-converting enzyme, which degrades Abeta. The activities of other Abeta-degrading enzymes, insulin degrading enzyme and neprilysin, were unchanged. These results indicate that increased neuronal PKCepsilon activity can promote Abeta clearance and reduce AD neuropathology through increased endothelin-converting enzyme activity.
Additional Information:
