DOI: 10.1002/mds.10229. Riluzole prolongs survival time and alters nuclear inclusion formation in a transgenic mouse model of Huntington's disease

Riluzole prolongs survival time and alters nuclear inclusion formation in a transgenic mouse model of Huntington's disease

10.1002/mds.10229

Crossref journal-article

Wiley

Movement Disorders (311)

Abstract

AbstractGlutamate excitotoxicity has been suggested to contribute to the pathogenesis of Huntington's disease (HD). Riluzole is a substance with glutamate antagonistic properties that is used for neuroprotective treatment in amyotrophic lateral sclerosis and which is currently tested in clinical trials for treatment of HD. R6/2 transgenic mice, which express exon 1 of the human HD gene with an expanded CAG triplet repeat, serve as a well‐characterized mouse model for HD with progressing neurological abnormalities and limited survival. We treated R6/2 HD transgenic mice with riluzole orally beginning at a presymptomatic stage until death to investigate its potential neuroprotective effects in this mouse model and found that survival time in the riluzole group was significantly increased in comparison to placebo‐treated transgenic controls. Additionally, the progressive weight loss was delayed and significantly reduced by riluzole treatment; behavioral testing of motor coordination and spontaneous locomotor activity, however, showed no statistically significant differences. We also examined the formation of the HD characteristic neuronal intranuclear inclusions (NII) immunohistologically. At a late disease stage, striatal NII from riluzole‐treated transgenic mice showed profound changes in ubiquitination, i.e., NII were less ubiquitinated and surrounded by ubiquitinated micro‐aggregates. Staining with antibodies directed against the mutated huntingtin revealed no significant difference in this component of NII. Taken together, these data suggest that riluzole is a promising candidate for neuroprotective treatment in human HD. © 2002 Movement Disorder Society

Bibliography

Schiefer, J., Landwehrmeyer, G. B., LÃ¼esse, H., SprÃ¼nken, A., Puls, C., Milkereit, A., Milkereit, E., & Kosinski, C. M. (2002). Riluzole prolongs survival time and alters nuclear inclusion formation in a transgenic mouse model of Huntingtonâs disease. Movement Disorders, 17(4), 748â757. Portico.

Authors 8

Johannes Schiefer (first)
G. Bernhard Landwehrmeyer (additional)
Hans‐Gerd Lüesse (additional)
Arne Sprünken (additional)
Christiane Puls (additional)
Anna Milkereit (additional)
Eva Milkereit (additional)
Christoph M. Kosinski (additional)

References 41 Referenced 95

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Dates

Type	When
Created	22 years, 10 months ago (Oct. 6, 2002, 7:44 a.m.)
Deposited	1 year, 10 months ago (Oct. 17, 2023, 6:20 a.m.)
Indexed	1 month ago (Aug. 2, 2025, 12:39 a.m.)
Issued	23 years, 2 months ago (July 1, 2002)
Published	23 years, 2 months ago (July 1, 2002)
Published Online	23 years, 1 month ago (July 22, 2002)
Published Print	23 years, 2 months ago (July 1, 2002)

Funders 0

None

BibTeX

@article{Schiefer_2002, title={Riluzole prolongs survival time and alters nuclear inclusion formation in a transgenic mouse model of Huntington’s disease}, volume={17}, ISSN={1531-8257}, url={http://dx.doi.org/10.1002/mds.10229}, DOI={10.1002/mds.10229}, number={4}, journal={Movement Disorders}, publisher={Wiley}, author={Schiefer, Johannes and Landwehrmeyer, G. Bernhard and Lüesse, Hans‐Gerd and Sprünken, Arne and Puls, Christiane and Milkereit, Anna and Milkereit, Eva and Kosinski, Christoph M.}, year={2002}, month=jul, pages={748–757} }

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