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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2(4):300-308;2009.
Original Article
Caspase activation in transgenic mice with Alzheimer-like pathology: results from a
pilot study utilizing the caspase inhibitor, Q-VD-OPh
Troy T. Rohn, Polina Kokoulina, Cody R. Eaton, Wayne W. Poon
Department of Biology, Science/Nursing Building, Room 228, Boise State University, Boise, Idaho, 83725, USA; Institute for Memory
Impairments and Neurological Disorders, University of California, Irvine, CA, USA
Received July 15, 2009; accepted October 30, 2009; available online November 5, 2009
Abstract: Despite the wealth of evidence supporting the activation of caspases in Alzheimer’s disease (AD), chron-ic administration of
a caspase inhibitor has never been tested in any animal model system. The purpose of the current report was to identify a suitable
animal model that displays caspase activation and cleavage of critical proteins associated with AD, and secondly, to undertake a pilot
study utilizing the novel caspase inhibitor, qui-nolyl-valyl-O-methylaspartyl-[-2, 6-difluorophenoxy]-methyl ketone (Q-VD-OPh). Analysis of
12 month-old TgCRND8 mice, which represent an early-onset animal model for AD, indicated the activation of caspase-7 as well as
the cleavage of tau and the amyloid precursor protein (APP). Having established that TgCRND8 mice represent a suit-able model
system to target caspases therapeutically, a prophylactic study was initiated utilizing Q-VD-OPh. Three month-old TgCRND8 mice were
injected intraperitoneally three times a week for three months with 10 mg/kg Q-VD-OPh and compared to control mice injected with
vehicle. Although there was no apparent effect on extracellu-lar A deposition, chronic treatment with Q-VD-OPh did prevent caspase-7
activation and limited the pathological changes associated with tau, including caspase cleavage. These preliminary findings suggest
that further studies examining the utility of Q-VD-OPh as a potential therapeutic compound for the treatment of AD are warranted.
(IJCEM910002).
Key words: Caspase; TgCRND8 mice, Alzheimer’s disease, Q-VD-OPh, amyloid, tau
Full Text PDF
Address all correspondence to:
Troy T. Rohn, PhD
Department of Biology
Science/Nursing Building, Room 228
Boise State University
Boise, Idaho, 83725
Tel: 208-426-2396, Fax: 208-426-4267
E-mail: trohn@boisestate.edu
Original Article
Caspase activation in transgenic mice with Alzheimer-like pathology: results from a
pilot study utilizing the caspase inhibitor, Q-VD-OPh
Troy T. Rohn, Polina Kokoulina, Cody R. Eaton, Wayne W. Poon
Department of Biology, Science/Nursing Building, Room 228, Boise State University, Boise, Idaho, 83725, USA; Institute for Memory
Impairments and Neurological Disorders, University of California, Irvine, CA, USA
Received July 15, 2009; accepted October 30, 2009; available online November 5, 2009
Abstract: Despite the wealth of evidence supporting the activation of caspases in Alzheimer’s disease (AD), chron-ic administration of
a caspase inhibitor has never been tested in any animal model system. The purpose of the current report was to identify a suitable
animal model that displays caspase activation and cleavage of critical proteins associated with AD, and secondly, to undertake a pilot
study utilizing the novel caspase inhibitor, qui-nolyl-valyl-O-methylaspartyl-[-2, 6-difluorophenoxy]-methyl ketone (Q-VD-OPh). Analysis of
12 month-old TgCRND8 mice, which represent an early-onset animal model for AD, indicated the activation of caspase-7 as well as
the cleavage of tau and the amyloid precursor protein (APP). Having established that TgCRND8 mice represent a suit-able model
system to target caspases therapeutically, a prophylactic study was initiated utilizing Q-VD-OPh. Three month-old TgCRND8 mice were
injected intraperitoneally three times a week for three months with 10 mg/kg Q-VD-OPh and compared to control mice injected with
vehicle. Although there was no apparent effect on extracellu-lar A deposition, chronic treatment with Q-VD-OPh did prevent caspase-7
activation and limited the pathological changes associated with tau, including caspase cleavage. These preliminary findings suggest
that further studies examining the utility of Q-VD-OPh as a potential therapeutic compound for the treatment of AD are warranted.
(IJCEM910002).
Key words: Caspase; TgCRND8 mice, Alzheimer’s disease, Q-VD-OPh, amyloid, tau
Full Text PDF
Address all correspondence to:
Troy T. Rohn, PhD
Department of Biology
Science/Nursing Building, Room 228
Boise State University
Boise, Idaho, 83725
Tel: 208-426-2396, Fax: 208-426-4267
E-mail: trohn@boisestate.edu
