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

Shanshan Hu, Meigui Hu, Jian Liu, Bei Zhang, Zhen Zhang, Fiona H. Zhou, Liping Wang, Jianghui Dong

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Purpose: 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 immunohisto-chemical 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 upregu-lated 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.

Original languageEnglish
Pages (from-to)651-663
Number of pages13
JournalNeuropsychiatric Disease and Treatment
Volume16
DOIs
Publication statusPublished - 2020

Keywords

  • Parkinson’s disease
  • Tau phosphorylation
  • α-Synuclein phosphorylation

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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