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Dimebon does not ameliorate pathological changes caused by expression of truncated (1-120) human alpha-synuclein in dopaminergic neurons of transgenic mice

Shelkovnikova, Tatyana, Ustyugov, Alexey, Millership, Steven, Peters, Owen Morgan, Anichtchik, Oleg, Spillantini, Maria Grazia, Buchman, Vladimir L., Bachurin, Sergey and Ninkina, Natalia 2011. Dimebon does not ameliorate pathological changes caused by expression of truncated (1-120) human alpha-synuclein in dopaminergic neurons of transgenic mice. Neurodegenerative Diseases 8 (6) , pp. 430-437. 10.1159/000324989

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Abstract

Background: Recent clinical studies have demonstrated that dimebon, a drug originally designed and used as a non-selective antihistamine, ameliorates symptoms and delays progress of mild to moderate forms of Alzheimer’s and Huntington’s diseases. Although the mechanism of dimebon action on pathological processes in degenerating brain is elusive, results of studies carried out in cell cultures and animal models suggested that this drug might affect the process of pathological accumulation and aggregation of various proteins involved in the pathogenesis of proteinopathies. However, the effect of this drug on the pathology caused by overexpression and aggregation of alpha-synuclein, including Parkinson’s disease (PD), has not been assessed. Objective: To test if dimebon affected alpha-synuclein-induced pathology using a transgenic animal model. Methods: We studied the effects of chronic dimebon treatment on transgenic mice expressing the C-terminally truncated (1–120) form of human alpha-synuclein in dopaminergic neurons, a mouse model that recapitulates several biochemical, histopathological and behavioral characteristics of the early stage of PD. Results: Dimebon did not improve balance and coordination of aging transgenic animals or increase the level of striatal dopamine, nor did it prevent accumulation of alpha-synuclein in cell bodies of dopaminergic neurons. Conclusion: Our observations suggest that in the studied model of alpha-synucleinopathy dimebon has very limited effect on certain pathological alterations typical of PD and related diseases.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Uncontrolled Keywords: dimebon; transgenic mouse model; α-synuclein; Parkinson’s disease; preclinical drug testing
Publisher: Karger
ISSN: 1660-2862
Last Modified: 07 Feb 2018 21:43
URI: http://orca.cf.ac.uk/id/eprint/24148

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