1. Academic Validation
  2. Apelin-13 protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through inhibiting endoplasmic reticulum stress and promoting autophagy

Apelin-13 protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through inhibiting endoplasmic reticulum stress and promoting autophagy

  • Brain Res. 2019 Jul 15;1715:203-212. doi: 10.1016/j.brainres.2019.03.027.
Junge Zhu 1 Shanshan Dou 2 Yunlu Jiang 2 Jing Chen 2 Chunmei Wang 3 Baohua Cheng 4
Affiliations

Affiliations

  • 1 Cheeloo College of Medicine, Shandong University, 250014 Jinan, China.
  • 2 Neurobiology Institute, Jining Medical University, 272067 Jining, China.
  • 3 Neurobiology Institute, Jining Medical University, 272067 Jining, China. Electronic address: wangchunmei410@163.com.
  • 4 Neurobiology Institute, Jining Medical University, 272067 Jining, China. Electronic address: chengbh1979@163.com.
Abstract

The dopaminergic neurodegeneration in the substantia nigrapars compacta (SNpc) and striatum of the midbrain is the important pathological feature of Parkinson's disease (PD). It has been shown that Autophagy and endoplasmic reticulum stress (ERS) are involved in the occurrence and development of PD. The neuropeptide Apelin-13 is neuroprotective in the neurological diseases such as PD, Alzheimer's disease and cerebral ischemic stroke. In the present work, we investigated the neuroprotective effects of Apelin-13 on ERS and Autophagy in the dopaminergic neurodegeneration of SNpc of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-treated mice. The intranigral injection of Apelin-13 alleviated the behavioral dysfunction and dopaminergic neurodegeneration induced by MPTP. After the exposure to MPTP, the expression of tyrosine hydroxylase (TH) was significantly decreased as well as the increased α-synuclein expression, which was significantly reversed by the intranigral injection of Apelin-13. Also, Apelin-13 significantly reversed the decreasing Autophagy induced by MPTP which was indicated by the up-regulation of LC3B-II and Beclin1 and down-regulation of p62. And MPTP-induced ERS such as IRE1α, XBP1s, CHOP and GRP78 was significantly inhibited by Apelin-13. Taken together, Apelin-13 protects dopaminergic neurons in MPTP-induced PD model mice in vivo through inhibiting ERS and promoting Autophagy, which contributes to the therapy for PD in the future.

Keywords

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridin; Apelin-13; Autophagy; Endoplasmic reticulum stress; Parkinson’s disease; α-Synuclein.

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