Evidence for dopaminergic axonal degeneration as an early pathological process in Parkinson's disease

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dc.contributor.authorO'Keeffe, Gerard W.
dc.contributor.authorSullivan, Aideen M.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2018-07-09T10:15:44Z
dc.date.available2018-07-09T10:15:44Z
dc.date.issued2018-06-19
dc.date.updated2018-07-09T09:26:30Z
dc.description.abstractParkinson's disease is a common neurodegenerative disorder presenting with a variety of motor and non-motor symptoms. The motor symptoms manifest as a result of the progressive degeneration of midbrain dopaminergic neurons. The axons of these neurons project to the striatum as the nigrostriatal pathway, which is a crucial part of the basal ganglia circuitry controlling movement. In addition to the neuronal degeneration, abnormal intraneuronal a-synuclein protein inclusions called Lewy bodies and Lewy neurites increase in number and spread throughout the nervous system as the disease progresses. While the loss of midbrain dopaminergic neurons is well-established as being central to motor symptoms, there is an increasing focus on the timing of nigrostriatal degeneration, with preclinical evidence suggesting that early axonal degeneration may play a key role in the early stages of Parkinson's disease. Here we review recent evidence for early midbrain dopaminergic axonal degeneration in patients with Parkinson's disease, and explore the potential role of a-synuclein accumulation in this process, with a focus on studies in human populations at the imaging, post-mortem, cellular and molecular levels. Finally, we discuss the implications of this for neurotrophic factor therapies for Parkinson's disease.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO'Keeffe, G. W. and Sullivan, A. M. (2018) 'Evidence for dopaminergic axonal degeneration as an early pathological process in Parkinson's disease', Parkinsonism and Related Disorders. doi:10.1016/j.parkreldis.2018.06.025en
dc.identifier.doi10.1016/j.parkreldis.2018.06.025
dc.identifier.issn1353-8020
dc.identifier.journaltitleParkinsonism and Related Disordersen
dc.identifier.urihttps://hdl.handle.net/10468/6433
dc.language.isoenen
dc.publisherElsevier Ltd.en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Career Development Award/15/CDA/3498/IE/Development of GDF5 neurotrophic factor therapy for Parkinson_s disease./en
dc.rights© 2018, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 licenseen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectParkinson's diseaseen
dc.subjectMidbrainen
dc.subjectAxonen
dc.subjectDegenerationen
dc.subjectAlpha-synucleinen
dc.subjectPatientsen
dc.titleEvidence for dopaminergic axonal degeneration as an early pathological process in Parkinson's diseaseen
dc.typeArticle (peer-reviewed)en
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