Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model
Abstract
Abstract Huntington disease ( HD ) is a neurodegenerative disorder for which new treatments are urgently needed. Pridopidine is a new dopaminergic stabilizer, recently developed for the treatment of motor symptoms associated with HD . The therapeutic effect of pridopidine in patients with HD has been determined in two double‐blind randomized clinical trials, however, whether pridopidine exerts neuroprotection remains to be addressed. The main goal of this study was to define the potential neuroprotective effect of pridopidine, in HD in vivo and in vitro models, thus providing evidence that might support a potential disease‐modifying action of the drug and possibly clarifying other aspects of pridopidine mode‐of‐action. Our data corroborated the hypothesis of neuroprotective action of pridopidine in HD experimental models. Administration of pridopidine protected cells from apoptosis, and resulted in highly improved motor performance in R6/2 mice. The anti‐apoptotic effect observed in the in vitro system highlighted neuroprotective properties of the drug, and advanced the idea of sigma‐1‐receptor as an additional molecular target implicated in the mechanism of action of pridopidine. Coherent with protective effects, pridopidine‐mediated beneficial effects in R6/2 mice were associated with an increased expression of pro‐survival and neurostimulatory molecules, such as brain derived neurotrophic factor and DARPP 32, and withmore »
- Authors:
-
- IRCCS Neuromed Pozzilli Italy
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1224661
- Alternate Identifier(s):
- OSTI ID: 1345705
- Resource Type:
- Published Article
- Journal Name:
- Journal of Cellular and Molecular Medicine
- Additional Journal Information:
- Journal Name: Journal of Cellular and Molecular Medicine Journal Volume: 19 Journal Issue: 11; Journal ID: ISSN 1582-1838
- Publisher:
- Wiley-Blackwell
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
Citation Formats
Squitieri, Ferdinando, Di Pardo, Alba, Favellato, Mariagrazia, Amico, Enrico, Maglione, Vittorio, and Frati, Luigi. Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model. Country unknown/Code not available: N. p., 2015.
Web. doi:10.1111/jcmm.12604.
Squitieri, Ferdinando, Di Pardo, Alba, Favellato, Mariagrazia, Amico, Enrico, Maglione, Vittorio, & Frati, Luigi. Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model. Country unknown/Code not available. https://doi.org/10.1111/jcmm.12604
Squitieri, Ferdinando, Di Pardo, Alba, Favellato, Mariagrazia, Amico, Enrico, Maglione, Vittorio, and Frati, Luigi. Mon .
"Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model". Country unknown/Code not available. https://doi.org/10.1111/jcmm.12604.
@article{osti_1224661,
title = {Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model},
author = {Squitieri, Ferdinando and Di Pardo, Alba and Favellato, Mariagrazia and Amico, Enrico and Maglione, Vittorio and Frati, Luigi},
abstractNote = {Abstract Huntington disease ( HD ) is a neurodegenerative disorder for which new treatments are urgently needed. Pridopidine is a new dopaminergic stabilizer, recently developed for the treatment of motor symptoms associated with HD . The therapeutic effect of pridopidine in patients with HD has been determined in two double‐blind randomized clinical trials, however, whether pridopidine exerts neuroprotection remains to be addressed. The main goal of this study was to define the potential neuroprotective effect of pridopidine, in HD in vivo and in vitro models, thus providing evidence that might support a potential disease‐modifying action of the drug and possibly clarifying other aspects of pridopidine mode‐of‐action. Our data corroborated the hypothesis of neuroprotective action of pridopidine in HD experimental models. Administration of pridopidine protected cells from apoptosis, and resulted in highly improved motor performance in R6/2 mice. The anti‐apoptotic effect observed in the in vitro system highlighted neuroprotective properties of the drug, and advanced the idea of sigma‐1‐receptor as an additional molecular target implicated in the mechanism of action of pridopidine. Coherent with protective effects, pridopidine‐mediated beneficial effects in R6/2 mice were associated with an increased expression of pro‐survival and neurostimulatory molecules, such as brain derived neurotrophic factor and DARPP 32, and with a reduction in the size of mHtt aggregates in striatal tissues. Taken together, these findings support the theory of pridopidine as molecule with disease‐modifying properties in HD and advance the idea of a valuable therapeutic strategy for effectively treating the disease.},
doi = {10.1111/jcmm.12604},
journal = {Journal of Cellular and Molecular Medicine},
number = 11,
volume = 19,
place = {Country unknown/Code not available},
year = {Mon Jun 22 00:00:00 EDT 2015},
month = {Mon Jun 22 00:00:00 EDT 2015}
}
https://doi.org/10.1111/jcmm.12604
Web of Science
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