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01-09-2009 | Basic Neurosciences, Genetics and Immunology - Original Article

Neuroprotective effects of probenecid in a transgenic animal model of Huntington’s disease

Authors: Eniko Vamos, Krisztina Voros, Denes Zadori, Laszlo Vecsei, Peter Klivenyi

Published in: Journal of Neural Transmission | Issue 9/2009

Abstract

Huntington’s disease (HD) is an autosomal dominantly inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin. The excitotoxicity, oxidative damage and altered membrane transport may have an important role in the pathogenesis of HD. Probenecid is a non-selective inhibitor of multidrug resistance-associated proteins, but it also inhibits organic anion transporters. In this study, we examined the effects of probenecid on the survival, behaviour and immunohistochemical changes in the N171-82Q transgenic mouse model of HD. After probenecid administration, the duration of survival improved by 35%. The motor activity was significantly ameliorated as compared with the control transgenic group. Probenecid treatment significantly reduced the neuronal loss and the number of neuronal intranuclear aggregates. These results suggest that probenecid may exert a neuroprotective effect by increasing the membrane transport of protective compounds, and/or inhibiting the toxic compounds.

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Title: Neuroprotective effects of probenecid in a transgenic animal model of Huntington’s disease
Authors: Eniko Vamos
Krisztina Voros
Denes Zadori
Laszlo Vecsei
Peter Klivenyi
Publication date: 01-09-2009
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 9/2009
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-009-0253-6

At a glance: The STEP trials

Springer Medicine

Neuroprotective effects of probenecid in a transgenic animal model of Huntington’s disease

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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