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Article
Caspase Activation in Transgenic Mice with Alzheimer-Like Pathology: Results from a Pilot Study Utilizing the Caspase Inhibitor, Q-VD-OPh
International Journal of Clinical and Experimental Medicine
  • Troy T. Rohn, Boise State University
  • Polina Kokoulina, Boise State University
  • Cody R. Eaton, Boise State University
  • Wayne W. Poon, Institute for Memory Impairments and Neurological Disorders
Document Type
Article
Publication Date
11-5-2009
Disciplines
Abstract
Despite the wealth of evidence supporting the activation of caspases in Alzheimer's disease (AD), chronic 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, quinolyl-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 suitable 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 extracellular Aβ 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.
Citation Information
Troy T. Rohn, Polina Kokoulina, Cody R. Eaton and Wayne W. Poon. "Caspase Activation in Transgenic Mice with Alzheimer-Like Pathology: Results from a Pilot Study Utilizing the Caspase Inhibitor, Q-VD-OPh" International Journal of Clinical and Experimental Medicine (2009)
Available at: http://works.bepress.com/troy_rohn/33/