Reference : Absence of regulator of G-protein signaling 4 does not protect against dopamine neuro...

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biotechnology Life sciences : Multidisciplinary, general & others Human health sciences : Neurology
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/31416

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
Language :	English
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) > >]
Publication date :	Oct-2017
Journal title :	Neurobiology of Aging
Publisher :	Elsevier
Volume :	58
Pages :	30-33
Peer reviewed :	Yes (verified by ORBilu)
Audience :	International
ISSN :	0197-4580
e-ISSN :	1558-1497
City :	New York
Country :	NY
Keywords :	[en] 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 centres :	Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Funders :	Fonds National de la Recherche - FnR
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
Target :	Researchers ; Professionals ; Students
Permalink :	http://hdl.handle.net/10993/31416
DOI :	10.1016/j.neurobiolaging.2017.06.008
Other URL :	http://www.sciencedirect.com/science/article/pii/S019745801730204X
Mentions required by the publisher for OA :	The original publication is available at http://www.sciencedirect.com/science/article/pii/S019745801730204X
FnR project :	FnR ; FNR5782168 > Enrico Glaab > ExPDIENT > Exploring Parkinson?s Disease Inhibitor Efficacy on a Non-dopaminergic Target > 01/12/2013 > 31/05/2016 > 2013

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