Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease.

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dc.contributor.authorO'Keefe, Gerard W.
dc.contributor.authorHegarty, Shane V.
dc.contributor.authorSullivan, Aideen M.
dc.contributor.funderIrish Research Councilen
dc.contributor.funderNational University of Irelanden
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2017-05-25T08:52:00Z
dc.date.available2017-05-25T08:52:00Z
dc.date.issued2017-03-31
dc.date.updated2017-05-23T10:19:50Z
dc.description.abstractParkinson's disease (PD) is the second most common neurodegenerative disease, characterized by the degeneration of midbrain dopaminergic (mDA) neurons and their axons, and aggregation of α-synuclein, which leads to motor and late-stage cognitive impairments. As the motor symptoms of PD are caused by the degeneration of a specific population of mDA neurons, PD lends itself to neurotrophic factor therapy. The goal of this therapy is to apply a neurotrophic factor that can slow down, halt or even reverse the progressive degeneration of mDA neurons. While the best known neurotrophic factors are members of the glial cell line-derived neurotrophic factor (GDNF) family, their lack of clinical efficacy to date means that it is important to continue to study other neurotrophic factors. Bone morphogenetic proteins (BMPs) are naturally secreted proteins that play critical roles during nervous system development and in the adult brain. In this review, we provide an overview of the BMP ligands, BMP receptors (BMPRs) and their intracellular signalling effectors, the Smad proteins. We review the available evidence that BMP–Smad signalling pathways play an endogenous role in mDA neuronal survival in vivo, before outlining how exogenous application of BMPs exerts potent effects on mDA neuron survival and axon growth in vitro and in vivo. We discuss the molecular mechanisms that mediate these effects, before highlighting the potential of targeting the downstream effectors of BMP–Smad signalling as a novel neuroprotective approach to slow or stop the degeneration of mDA neurons in PD.en
dc.description.sponsorshipIrish Research Council (grant number R15897); National University of Ireland (grant number R16189); Science Foundation Ireland (SFI grant number 15/CDA/13498)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleidNS20170027
dc.identifier.citationO'Keeffe, Gerard W., Hegarty, Shane V. and Sullivan, Aideen M. (2017) 'Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease', Neuronal Signaling, 1(2). doi: 10.1042/ns20170027en
dc.identifier.doi10.1042/NS20170027
dc.identifier.endpageNS20170027-11en
dc.identifier.issn2059-6553
dc.identifier.issued2en
dc.identifier.journaltitleNeuronal Signalingen
dc.identifier.startpageNS20170027-1en
dc.identifier.urihttps://hdl.handle.net/10468/4022
dc.identifier.volume1en
dc.language.isoenen
dc.publisherPortland Pressen
dc.rights© 2017 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY).en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectAxonen
dc.subjectBone morphogenetic proteinen
dc.subjectDopamineen
dc.subjectNeuronen
dc.subjectNeuroprotectionen
dc.subjectNeurotrophic factoren
dc.subjectParkinson's diseaseen
dc.subjectSmaden
dc.titleTargeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease.en
dc.typeArticle (peer-reviewed)en
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