| Caspase activation in transgenic mice with Alzheimer-like pathology: results from a pilot study utilizing the caspase inhibitor, Q-VD-OPh. | |
| | |
MedLine Citation:
|
PMID: 20057974 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Troy T Rohn; Polina Kokoulina; Cody R Eaton; Wayne W Poon |
Related Documents
:
|
15056724 - Abnormality of g-protein-coupled receptor kinases at prodromal and early stages of alzh... 19394434 - Ccr5 deficiency induces astrocyte activation, abeta deposit and impaired memory function. 16926764 - Tnf-alpha modulation for treatment of alzheimer's disease: a 6-month pilot study. 16469784 - Effects of secreted oligomers of amyloid beta-protein on hippocampal synaptic plasticit... 15023794 - Facial nerve recovery in bcl2 overexpression mice after crush injury. 9552164 - Nicotine blocks tnf-alpha-mediated neuroprotection to nmda by an alpha-bungarotoxin-sen... |
Publication Detail:
|
Type: Journal Article Date: 2009-11-05 |
Journal Detail:
|
Title: International journal of clinical and experimental medicine Volume: 2 ISSN: 1940-5901 ISO Abbreviation: Int J Clin Exp Med Publication Date: 2009 |
Date Detail:
|
Created Date: 2010-01-08 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101471010 Medline TA: Int J Clin Exp Med Country: United States |
Other Details:
|
Languages: eng Pagination: 300-8 Citation Subset: - |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Polymorphisms in the survivin promoter are associated with age of onset of ovarian cancer.
Next Document: Acid stress response of a mycobacterial proteome: insight from a gene ontology analysis.