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Chronic administration of dimebon does not ameliorate amyloid-β pathology in 5xFAD transgenic mice

Peters, Owen Morgan, Shelkovnikova, Tatyana, Tarasova, Tatiana, Springe, Signe, Kukharsky, Michail S., Smith, Gaynor A., Brooks, Simon Philip, Kozin, Sergey A., Kotelevtsev, Yury, Bachurin, Sergey O., Ninkina, Natalia and Buchman, Vladimir L. 2013. Chronic administration of dimebon does not ameliorate amyloid-β pathology in 5xFAD transgenic mice. Journal of Alzheimer's Disease 36 (3) , pp. 589-596. 10.3233/JAD-130071

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Abstract

Dimebon has been tested as a potential modifier of Alzheimer's disease (AD), resulting in mixed clinical trial outcomes. Originally utilized as an antihistamine, Dimebon was later found to ameliorate AD symptoms in initial human trials. Although subsequent trials have reportedly failed to replicate these finding, there is a growing body of evidence that Dimebon might be neuroprotective in certain models of neurodegeneration. The precise mechanism by which Dimebon is thought to act in AD is unclear, though changes in receptor activity, mitochondria function, and autophagy activity have been proposed. It is thus necessary to test Dimebon in transgenic animal model systems to determine if and how the drug affects development and manifestation of pathology, and which pathogenic processes are altered. In the present study we treated mice harboring five familial mutations associated with hereditary AD (5xFAD line) with a chronic regime of Dimebon. The compound was not found to improve the general health or motor behavior of these mice, nor prevent accumulation of Aβ peptides in the brain. Modest changes in response to an anxiogenic task were, however, detected, suggesting Dimebon might improve behavioral abnormalities and cognition in disease in a mechanism independent of protecting against amyloidosis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QR Microbiology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Alzheimer's disease, dimebolin, latrepirdine, tauopathy, therapeutics, transgenic mice
Publisher: IOS Press
ISSN: 1387-2877
Last Modified: 28 Jun 2019 02:08
URI: http://orca.cf.ac.uk/id/eprint/57133

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