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

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dc.contributor.author O'Keefe, Gerard W.
dc.contributor.author Hegarty, Shane V.
dc.contributor.author Sullivan, Aideen M.
dc.date.accessioned 2017-05-25T08:52:00Z
dc.date.available 2017-05-25T08:52:00Z
dc.date.issued 2017-03-31
dc.identifier.citation O'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/ns20170027 en
dc.identifier.volume 1 en
dc.identifier.issued 2 en
dc.identifier.startpage NS20170027-1 en
dc.identifier.endpage NS20170027-11 en
dc.identifier.issn 2059-6553
dc.identifier.uri http://hdl.handle.net/10468/4022
dc.identifier.doi 10.1042/NS20170027
dc.description.abstract Parkinson'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.sponsorship Irish Research Council (grant number R15897); National University of Ireland (grant number R16189); Science Foundation Ireland (SFI grant number 15/CDA/13498) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Portland Press en
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.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Axon en
dc.subject Bone morphogenetic protein en
dc.subject Dopamine en
dc.subject Neuron en
dc.subject Neuroprotection en
dc.subject Neurotrophic factor en
dc.subject Parkinson's disease en
dc.subject Smad en
dc.title Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease. en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Shane Hegarty, Department Of Anatomy & Neuroscience, University College Cork, Cork, Ireland. +353-21-490-3000 Email: shane.hegarty@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2017-05-23T10:19:50Z
dc.description.version Published Version en
dc.internal.rssid 385199621
dc.contributor.funder Irish Research Council en
dc.contributor.funder National University of Ireland en
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Neuronal Signaling en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress shane.hegarty@ucc.ie en
dc.identifier.articleid NS20170027


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© 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). Except where otherwise noted, this item's license is described as © 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).
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