1. Academic Validation
  2. Caspase activation in transgenic mice with Alzheimer-like pathology: results from a pilot study utilizing the caspase inhibitor, Q-VD-OPh

Caspase activation in transgenic mice with Alzheimer-like pathology: results from a pilot study utilizing the caspase inhibitor, Q-VD-OPh

  • Int J Clin Exp Med. 2009 Nov 5;2(4):300-8.
Troy T Rohn Polina Kokoulina Cody R Eaton Wayne W Poon
PMID: 20057974
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 Abeta 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.

Keywords

Alzheimer's disease; Caspase; Q-VD-OPh; TgCRND8 mice; amyloid; tau.

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