期刊
NEURODEGENERATIVE DISEASES
卷 8, 期 6, 页码 430-437出版社
KARGER
DOI: 10.1159/000324989
关键词
Dimebon; Transgenic mouse model; alpha-Synuclein; Parkinson's disease; Preclinical drug testing
资金
- Russian Foundation for Basic Research
- RAS
- Alzheimer's Society
- Wellcome Trust [075615/Z/04/z]
- Parkinson"
- s UK [G-0701] Funding Source: researchfish
- Alzheimer"
- s Society [116] Funding Source: researchfish
Background: Recent clinical studies have demonstrated that dimebon, a drug originally designed and used as a nonselective 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. Copyright (C) 2011 S. Karger AG, Basel
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