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dc.contributor.authorAshrafi, Amer
dc.contributor.authorGarcia, Pierre
dc.contributor.authorKollmus, Heike
dc.contributor.authorSchughart, Klaus
dc.contributor.authorDel Sol, Antonio
dc.contributor.authorButtini, Manuel
dc.contributor.authorGlaab, Enrico
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.
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
refterms.dateFOA2018-06-12T18:05:58Z
html.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.


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