Protocol for evaluation of neurotrophic strategies in Parkinson's disease-related dopaminergic and sympathetic neurons in vitro

dc.contributor.authorHegarty, Shane V.
dc.contributor.authorSullivan, Aideen M.
dc.contributor.authorO'Keeffe, Gerard W.
dc.contributor.funderIrish Research Councilen
dc.contributor.funderNational University of Irelanden
dc.date.accessioned2017-02-13T16:12:16Z
dc.date.available2017-02-13T16:12:16Z
dc.date.issued2016-07-25
dc.date.updated2017-02-13T16:02:53Z
dc.description.abstractParkinson’s disease (PD) is a neurodegenerative disease that is characterised by motor and non-motor symptoms which result from the progressive degeneration of nigrostriatal ventral midbrain (VM) dopaminergic (DA) neurons, as well as peripheral sympathetic neurons. PD is incurable, with current therapeutic strategies providing symptomatic relief. Neurotrophic factor (NTF) therapy has the potential to protect degenerating neurons in PD. However, there has been limited success in PD clinical trials due to neurotrophic strategies that are invasive, inefficient in delivering sustained neurotrophic support, do not protect all degenerating neurons and may have a compromised mechanism of action in the PD brain. Therefore, while neurotrophic therapy remains a promising disease-modifying approach for PD, it is important to identify novel neurotrophic strategies that can protect all neurons affected by PD. To address this need, we report an integrated approach for pre-clinical evaluation of potential neurotrophic strategies, e.g., pharmacological agents (e.g., drugs/small molecules), signalling proteins (e.g., morphogens) and/or genetic (gene/mRNA) modifications, in cellular models of the neuronal populations that are affected by PD. Herein, we describe, in detail, an in vitro protocol that allows a step-wise evaluation of the efficacy, and mechanism(s) of action, of novel neurotrophic strategies in VM DA neurons and sympathetic neurons, following an initial evaluation in a human cell line model of these cells, SH-SY5Y cells. The protocol uses the induction of neurite growth as the primary measure of neurotrophic action. Indeed, the neuro-protection/-restoration of PD-affected axons is widely thought to be an appropriate target for effective therapeutic intervention in PD.en
dc.description.sponsorshipIrish Research Council (R15897); National University of Ireland (R16189)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHegarty, S. V., Sullivan, A. M. and O'Keeffe, G. W. (2016) 'Protocol for evaluation of neurotrophic strategies in Parkinson's disease-related dopaminergic and sympathetic neurons in vitro'. Journal of Biological Methods, 3(3), e50. doi:10.14440/jbm.2016.124en
dc.identifier.doi10.14440/jbm.2016.124
dc.identifier.endpagee50-11en
dc.identifier.issn2326-9901
dc.identifier.issued3en
dc.identifier.journaltitleJournal of Biological Methodsen
dc.identifier.startpagee50-1en
dc.identifier.urihttps://hdl.handle.net/10468/3624
dc.identifier.volume3en
dc.language.isoenen
dc.publisherPOL Scientificen
dc.relation.urihttp://www.jbmethods.org/jbm/article/view/124
dc.rights© 2016, The Authors. Published by POL Scientific LLC. This work is licensed under a Creative Commons Attribution 3.0 License.en
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/en
dc.subjectNeurite growth analysisen
dc.subjectDopaminergic neuronen
dc.subjectNeurotrophic therapyen
dc.subjectSympathetic neuronen
dc.subjectParkinson's diseaseen
dc.titleProtocol for evaluation of neurotrophic strategies in Parkinson's disease-related dopaminergic and sympathetic neurons in vitroen
dc.typeArticle (peer-reviewed)en
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