Phosphorylation of Tau and α-Synuclein Induced Neurodegeneration in MPTP Mouse Model of Parkinson’s Disease

Shanshan Hu, 1,* Meigui Hu, 2,* Jian Liu, 3 Bei Zhang, 4 Zhen Zhang, 5 Fiona H Zhou, 6 Liping Wang, 5, 6 Jianghui Dong 5, 6 1Good Clinical Practice Center, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou, People’s Republic of China; 2The Second School of Clinical M...

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Autores principales: Hu S, Hu M, Liu J, Zhang B, Zhang Z, Zhou FH, Wang L, Dong J
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Publicado: Dove Medical Press 2020
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spelling oai:doaj.org-article:a31653c24ad34230a8ce0cfd94a853d72021-12-02T11:34:59ZPhosphorylation of Tau and α-Synuclein Induced Neurodegeneration in MPTP Mouse Model of Parkinson’s Disease1178-2021https://doaj.org/article/a31653c24ad34230a8ce0cfd94a853d72020-03-01T00:00:00Zhttps://www.dovepress.com/phosphorylation-of-tau-and-alpha-synuclein-induced-neurodegeneration-i-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Shanshan Hu, 1,* Meigui Hu, 2,* Jian Liu, 3 Bei Zhang, 4 Zhen Zhang, 5 Fiona H Zhou, 6 Liping Wang, 5, 6 Jianghui Dong 5, 6 1Good Clinical Practice Center, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou, People’s Republic of China; 2The Second School of Clinical Medicine, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, Guangdong, People’s Republic of China; 3Department of Anatomy, Zunyi Medical University, Zunyi 563000, Guizhou, People’s Republic of China; 4Department of Stomatology, The First People’s Hospital of Zunyi, Zunyi 563099, Guizhou, People’s Republic of China; 5Department of Hand Surgery, Department of Plastic Reconstructive Surgery, Ningbo No. 6 Hospital, Ningbo 315040, People’s Republic of China; 6School of Pharmacy and Medical Sciences, and UniSA Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia*These authors contributed equally to this workCorrespondence: Jianghui Dong; Liping WangDepartment of Hand Surgery, Ningbo No. 6 Hospital, Ningbo 315040, People’s Republic of ChinaTel +618 8302 2715Fax +618 8302 1087Email Jianghui.dong@mymail.unisa.edu.au; liping.wang@unisa.edu.auPurpose: 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.Keywords: α-Synuclein phosphorylation, Tau phosphorylation, Parkinson’s diseaseHu SHu MLiu JZhang BZhang ZZhou FHWang LDong JDove Medical Pressarticleα-synuclein phosphorylationtau phosphorylationparkinson’s diseaseNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 651-663 (2020)
institution DOAJ
collection DOAJ
language EN
topic α-synuclein phosphorylation
tau phosphorylation
parkinson’s disease
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle α-synuclein phosphorylation
tau phosphorylation
parkinson’s disease
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Hu S
Hu M
Liu J
Zhang B
Zhang Z
Zhou FH
Wang L
Dong J
Phosphorylation of Tau and α-Synuclein Induced Neurodegeneration in MPTP Mouse Model of Parkinson’s Disease
description Shanshan Hu, 1,* Meigui Hu, 2,* Jian Liu, 3 Bei Zhang, 4 Zhen Zhang, 5 Fiona H Zhou, 6 Liping Wang, 5, 6 Jianghui Dong 5, 6 1Good Clinical Practice Center, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou, People’s Republic of China; 2The Second School of Clinical Medicine, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, Guangdong, People’s Republic of China; 3Department of Anatomy, Zunyi Medical University, Zunyi 563000, Guizhou, People’s Republic of China; 4Department of Stomatology, The First People’s Hospital of Zunyi, Zunyi 563099, Guizhou, People’s Republic of China; 5Department of Hand Surgery, Department of Plastic Reconstructive Surgery, Ningbo No. 6 Hospital, Ningbo 315040, People’s Republic of China; 6School of Pharmacy and Medical Sciences, and UniSA Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia*These authors contributed equally to this workCorrespondence: Jianghui Dong; Liping WangDepartment of Hand Surgery, Ningbo No. 6 Hospital, Ningbo 315040, People’s Republic of ChinaTel +618 8302 2715Fax +618 8302 1087Email Jianghui.dong@mymail.unisa.edu.au; liping.wang@unisa.edu.auPurpose: 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.Keywords: α-Synuclein phosphorylation, Tau phosphorylation, Parkinson’s disease
format article
author Hu S
Hu M
Liu J
Zhang B
Zhang Z
Zhou FH
Wang L
Dong J
author_facet Hu S
Hu M
Liu J
Zhang B
Zhang Z
Zhou FH
Wang L
Dong J
author_sort Hu S
title Phosphorylation of Tau and α-Synuclein Induced Neurodegeneration in MPTP Mouse Model of Parkinson’s Disease
title_short Phosphorylation of Tau and α-Synuclein Induced Neurodegeneration in MPTP Mouse Model of Parkinson’s Disease
title_full Phosphorylation of Tau and α-Synuclein Induced Neurodegeneration in MPTP Mouse Model of Parkinson’s Disease
title_fullStr Phosphorylation of Tau and α-Synuclein Induced Neurodegeneration in MPTP Mouse Model of Parkinson’s Disease
title_full_unstemmed Phosphorylation of Tau and α-Synuclein Induced Neurodegeneration in MPTP Mouse Model of Parkinson’s Disease
title_sort phosphorylation of tau and α-synuclein induced neurodegeneration in mptp mouse model of parkinson’s disease
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/a31653c24ad34230a8ce0cfd94a853d7
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