Phosphorylation of tau and α-synuclein induced neurodegeneration in MPTP mouse model of Parkinson’s disease

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dc.contributor.authorHu, S.
dc.contributor.authorHu, M.
dc.contributor.authorLiu, J.
dc.contributor.authorZhang, B.
dc.contributor.authorZhang, Z.
dc.contributor.authorZhou, F.H.
dc.contributor.authorWang, L.
dc.contributor.authorDong, J.
dc.date.issued2020
dc.description.abstractPurpose: Parkinson’s disease (PD) is the second most common neurodegenerative disease. The α-Synuclein is a major component of Lewy bodies and Lewy neurites, the pathologic hallmark of PD. It is known that α-Synuclein is phosphorylated (p-α-Synuclein) in PD and tau-hyperphosphorylation (p-Tau) is also a pathologic feature of PD. However, the relationship between p-Synuclein and p-Tau in PD is not clear, in particular in the MPTP model of PD. The purpose of this study was to reveal their relationship in the mouse MPTP model. Methods: Firstly, the p-α-Synuclein, α-Synuclein, p-Tau and Tau protein levels were analyzed. Then, GSK3β activation was determined using immunoblot and immunohistochemical staining. Finally, the dopaminergic neurodegeneration was assessed using Tyrosine Hydroxylase (TH) staining and retrograde labeling and microglial marker were labeled. Microglial activation and nigrostriatal pathway degeneration were observed. Results: The results showed that p-α-Synuclein, α-Synuclein, p-Tau and Tau were upregulated in both hippocampus and substantia nigra of the PD mouse model. Furthermore, p-α- Synuclein and p-Tau were localized in the same regions of substantial nigra (SN) and dentate gyrus (DG) of hippocampus (Hippo). The activated form of GSK3β (phosphor GSK3β Y216) was increased in multiple brain areas. The GSK3β inhibitor AZD1080 injected in MPTP mice suppressed the expression of p-Tau and p-GSK3β and improved motor functions. Conclusion: These findings revealed that p-α-Synuclein and p-Tau proteins are key pathological events leading to neurodegeneration and motor dysfunctions in the mouse MPTP model of PD. Our data suggest that the interference with the GSK3β activity may be an effective approach for the treatment of PD.
dc.description.statementofresponsibilityShanshan Hu, Meigui Hu, Jian Liu, Bei Zhang, Zhen Zhang, Fiona H Zhou, Liping Wang, Jianghui Dong
dc.identifier.citationNeuropsychiatric Disease and Treatment, 2020; 16:651-663
dc.identifier.doi10.2147/NDT.S235562
dc.identifier.issn1176-6328
dc.identifier.issn1178-2021
dc.identifier.orcidZhou, F.H. [0000-0003-3113-1671]
dc.identifier.urihttps://hdl.handle.net/2440/146455
dc.language.isoen
dc.publisherDove Medical Press
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1158402
dc.rights© 2020 Hu et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
dc.source.urihttps://doi.org/10.2147/ndt.s235562
dc.subjectα-Synuclein phosphorylation; Tau phosphorylation; Parkinson’s disease
dc.titlePhosphorylation of tau and α-synuclein induced neurodegeneration in MPTP mouse model of Parkinson’s disease
dc.typeJournal article
pubs.publication-statusPublished

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