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Article

Rg1 exhibits neuroprotective effects by inhibiting the endoplasmic reticulum stress‑mediated c‑Jun N‑terminal protein kinase apoptotic pathway in a rat model of Alzheimer's disease

  • Authors:
    • Jun‑Shan Mu
    • Hang Lin
    • Jian‑Xin Ye
    • Min Lin
    • Xiao‑Ping Cui
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, Fuzhou General Hospital and Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350025 P.R. China
  • Pages: 3862-3868
    |
    Published online on: May 27, 2015
       https://doi.org/10.3892/mmr.2015.3853
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Abstract

The neuroprotective agents currently used to treat Alzheimer's disease (AD) often only target one aspect of the disease process. Therefore, identifying effective drug targets associated with the pathogenesis of AD is critical for the production of novel AD therapeutic strategies. The present study aimed to investigate the underlying mechanisms of the neuroprotective effects of Rg1 on a rat model of AD. A double transgenic β‑amyloid (Aβ) precursor protein/PS1 rat model was established, which co‑expressed mutations associated with AD. Aβ plaques and neurofibrillary tangles (NFTs) were detected by immunohistochemistry. The detection of the protein expression levels of caspase‑3 and terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling (TUNEL) staining were used to determine the level of apoptosis in the brain tissue. The expression levels of the endoplasmic reticulum (ER) stress biomarker, glucose‑regulated protein 78 (Grp78), and the mitochondrial apoptosis biomarkers, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax), were analyzed by western blotting. Furthermore, the expression of the proteins associated with the ER stress unfolded protein response (UPR) was determined, in order to examine the levels of ER stress. The mRNA expression of downstream genes of UPR were also detected by reverse transcription‑polymerase chain reaction. The protein expression levels of the apoptosis‑associated phosphorylated‑c‑Jun N‑terminal protein kinase (p‑JNK), caspase‑12 and cAMP response element‑binding transcription factor homologous protein were determined by western blotting. The results of the present study indicated that the accumulation of NFTs and Aβ plaques was significantly decreased in the Rg1‑treated AD rats, compared with untreated AD rats. The expression of caspase‑3 and the number of TUNEL‑positive cells were also significantly decreased in the Rg1‑treated rats, as compared with the AD rats. Furthermore, treatment with Rg1 significantly reduced the expression of Grp78, and triggered inositol‑requiring enzyme‑1 (IRE‑1) and phosphorylated protein kinase RNA‑like ER kinase‑associated ER stress. The IRE‑1 UPR pathway downstream gene, tumor necrosis factor receptor‑associated factor 2, was significantly decreased in rats treated with Rg1, compared with untreated AD rats. Furthermore, the activation of p‑JNK was also inhibited when AD rats were treated with Rg1. In conclusion, Rg1 was shown to function as an important factor that inhibits the accumulation of NFTs and Aβ via inhibition of the ER stress‑mediated pathway. Blocking of this pathway was triggered by the IRE‑1 and TRAF2 pathway, as a result of inhibition of the expression of p‑JNK.
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Copy and paste a formatted citation
Spandidos Publications style
Mu JS, Lin H, Ye JX, Lin M and Cui XP: Rg1 exhibits neuroprotective effects by inhibiting the endoplasmic reticulum stress‑mediated c‑Jun N‑terminal protein kinase apoptotic pathway in a rat model of Alzheimer's disease. Mol Med Rep 12: 3862-3868, 2015.
APA
Mu, J., Lin, H., Ye, J., Lin, M., & Cui, X. (2015). Rg1 exhibits neuroprotective effects by inhibiting the endoplasmic reticulum stress‑mediated c‑Jun N‑terminal protein kinase apoptotic pathway in a rat model of Alzheimer's disease. Molecular Medicine Reports, 12, 3862-3868. https://doi.org/10.3892/mmr.2015.3853
MLA
Mu, J., Lin, H., Ye, J., Lin, M., Cui, X."Rg1 exhibits neuroprotective effects by inhibiting the endoplasmic reticulum stress‑mediated c‑Jun N‑terminal protein kinase apoptotic pathway in a rat model of Alzheimer's disease". Molecular Medicine Reports 12.3 (2015): 3862-3868.
Chicago
Mu, J., Lin, H., Ye, J., Lin, M., Cui, X."Rg1 exhibits neuroprotective effects by inhibiting the endoplasmic reticulum stress‑mediated c‑Jun N‑terminal protein kinase apoptotic pathway in a rat model of Alzheimer's disease". Molecular Medicine Reports 12, no. 3 (2015): 3862-3868. https://doi.org/10.3892/mmr.2015.3853
Copy and paste a formatted citation
x
Spandidos Publications style
Mu JS, Lin H, Ye JX, Lin M and Cui XP: Rg1 exhibits neuroprotective effects by inhibiting the endoplasmic reticulum stress‑mediated c‑Jun N‑terminal protein kinase apoptotic pathway in a rat model of Alzheimer's disease. Mol Med Rep 12: 3862-3868, 2015.
APA
Mu, J., Lin, H., Ye, J., Lin, M., & Cui, X. (2015). Rg1 exhibits neuroprotective effects by inhibiting the endoplasmic reticulum stress‑mediated c‑Jun N‑terminal protein kinase apoptotic pathway in a rat model of Alzheimer's disease. Molecular Medicine Reports, 12, 3862-3868. https://doi.org/10.3892/mmr.2015.3853
MLA
Mu, J., Lin, H., Ye, J., Lin, M., Cui, X."Rg1 exhibits neuroprotective effects by inhibiting the endoplasmic reticulum stress‑mediated c‑Jun N‑terminal protein kinase apoptotic pathway in a rat model of Alzheimer's disease". Molecular Medicine Reports 12.3 (2015): 3862-3868.
Chicago
Mu, J., Lin, H., Ye, J., Lin, M., Cui, X."Rg1 exhibits neuroprotective effects by inhibiting the endoplasmic reticulum stress‑mediated c‑Jun N‑terminal protein kinase apoptotic pathway in a rat model of Alzheimer's disease". Molecular Medicine Reports 12, no. 3 (2015): 3862-3868. https://doi.org/10.3892/mmr.2015.3853
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