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.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621076
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.
Authors:
Ashrafi, Amer; Garcia, Pierre; Kollmus, Heike; Schughart, Klaus ( 0000-0002-6824-7523 ) ; Del Sol, Antonio; Buttini, Manuel; Glaab, Enrico
Abstract:
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 options 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 nondopaminergic 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 end points 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 nondopaminergic target for PD should be approached with caution.
Affiliation:
HelmholtzCentre of infetion research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
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. 2017, 58:30-33 Neurobiol. Aging
Journal:
Neurobiology of aging
Issue Date:
19-Jun-2017
URI:
http://hdl.handle.net/10033/621076
DOI:
10.1016/j.neurobiolaging.2017.06.008
PubMed ID:
28697377
Type:
Article
Language:
en
ISSN:
1558-1497
Appears in Collections:
publications of the department infection genetics (INFG)

Full metadata record

DC FieldValue Language
dc.contributor.authorAshrafi, Ameren
dc.contributor.authorGarcia, Pierreen
dc.contributor.authorKollmus, Heikeen
dc.contributor.authorSchughart, Klausen
dc.contributor.authorDel Sol, Antonioen
dc.contributor.authorButtini, Manuelen
dc.contributor.authorGlaab, Enricoen
dc.date.accessioned2017-08-28T12:57:40Z-
dc.date.available2017-08-28T12:57:40Z-
dc.date.issued2017-06-19-
dc.identifier.citationAbsence 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. 2017, 58:30-33 Neurobiol. Agingen
dc.identifier.issn1558-1497-
dc.identifier.pmid28697377-
dc.identifier.doi10.1016/j.neurobiolaging.2017.06.008-
dc.identifier.urihttp://hdl.handle.net/10033/621076-
dc.description.abstractRegulator 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 options 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 nondopaminergic 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 end points 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 nondopaminergic target for PD should be approached with caution.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleAbsence 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.en
dc.typeArticleen
dc.contributor.departmentHelmholtzCentre of infetion research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalNeurobiology of agingen

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