Article (Scientific journals)
Absence of regulator of G-protein signaling 4 does not protect against dopamine neuron dysfunction and injury in the mouse 6-hydroxydopamine lesion model of Parkinson's disease
Ashrafi, Amer; Garcia, Pierre; Kollmus, Heike et al.
2017In Neurobiology of Aging, 58, p. 30-33
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Keywords :
Parkinson's disease; mouse model; histopathology; behavior; neuroprotection; target validation; substantia nigra; RGS4; regulator of G-protein signaling
Abstract :
[en] Regulator of G-Protein Signaling 4 (RGS4), a member of the RGS family of proteins that inactivate G-proteins, has gained interest as a potential drug target for neurological disorders, such as epilepsy and Parkinson’s disease (PD). In the case of PD, the main current option for alleviating motor symptoms are dopamine replacement therapies, which have limitations because of side effects, and reduced effectiveness over the long term. Research on new non-dopaminergic PD drug targets has indicated that inhibition of RGS4 could be an effective adjuvant treatment option. The effectiveness of RGS4 inhibition for an array of PD-linked functional and structural neuroprotection endpoints has not yet been demonstrated. Here, we use the 6-Hydroxydopamine (6-OHDA) lesioning model of the nigrostriatal pathway in mice to address this question. We observe, using a battery of behavioral and pathological measures, that mice deficient for RGS4 are not protected from 6-OHDA induced injury, and show enhanced susceptibility in some measures of motor function. Our results suggest that inhibition of RGS4 as a non-dopaminergic target for PD should be approached with caution.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Disciplines :
Biotechnology
Neurology
Life sciences: Multidisciplinary, general & others
Author, co-author :
Ashrafi, Amer ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Garcia, Pierre  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Kollmus, Heike
Schughart, Klaus
del Sol Mesa, Antonio ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Buttini, Manuel ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Glaab, Enrico  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
External co-authors :
yes
Language :
English
Title :
Absence of regulator of G-protein signaling 4 does not protect against dopamine neuron dysfunction and injury in the mouse 6-hydroxydopamine lesion model of Parkinson's disease
Publication date :
October 2017
Journal title :
Neurobiology of Aging
ISSN :
1558-1497
Publisher :
Elsevier, New York, United States - New York
Volume :
58
Pages :
30-33
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
FnR Project :
FNR5782168 - Exploring Parkinson'S Disease Inhibitor Efficacy On A Non-dopaminergic Target, 2013 (01/12/2013-31/05/2016) - Enrico Glaab
Name of the research project :
R-AGR-0461-10 > ExPDIENT: Exploring Parkinson’s Disease Inhibitor Efficacy on Novel Targets > 01/12/2013 - 31/05/2016 > GLAAB Enrico
Funders :
FNR - Fonds National de la Recherche [LU]
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since 12 June 2017

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