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  2. Apelin-36 mitigates MPTP/MPP+-induced neurotoxicity: Involvement of α-synuclein and endoplasmic reticulum stress

Apelin-36 mitigates MPTP/MPP+-induced neurotoxicity: Involvement of α-synuclein and endoplasmic reticulum stress

  • Brain Res. 2019 Oct 15;1721:146334. doi: 10.1016/j.brainres.2019.146334.
Junge Zhu 1 Shanshan Dou 2 Chunmei Wang 2 Yunlu Jiang 2 Chuangong Wang 3 Baohua Cheng 4
Affiliations

Affiliations

  • 1 Cheeloo College of Medicine, Shandong University, 250014 Jinan, China; Neurobiology Institute, Jining Medical University, 272067 Jining, China.
  • 2 Neurobiology Institute, Jining Medical University, 272067 Jining, China.
  • 3 Neurobiology Institute, Jining Medical University, 272067 Jining, China. Electronic address: [email protected].
  • 4 Neurobiology Institute, Jining Medical University, 272067 Jining, China. Electronic address: [email protected].
Abstract

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons within the substantia nigra compacta (SNpc) which leads to the behavioral dysfunction. In the present study, we investigated the effect of Apelin-36 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)/1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity. The treatment with Apelin-36 significantly alleviated the MPTP-induced the behavioral dysfunction and dopaminergic neurodegeneration in the SNpc of mice, and also remarkably decreased the MPP+-induced cell death of SH-SY5Y cells. Furthermore, Apelin-36 reversed the MPTP/MPP+-induced loss of TH expression and the induction of α-synuclein expression. Additionally, Apelin-36 significantly attenuated the endoplasmic reticulum stress (ERS) indicated by the inhibition of GRP78, CHOP and cleaved caspase-12 expression in MPTP/MPP+ treated mice and cells. Taken together, the results indicated that Apelin-36 attenuates MPTP/MPP+-induced neurotoxicity, and suggested that Apelin-36 could be a potential therapeutic strategy for the treatment of PD.

Keywords

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridin; 1-Methyl-4-phenylpyridinium; Apelin-36; Endoplasmic reticulum stress; Parkinson’s disease.

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