Tripchlorolide attenuates β-amyloid generation by inducing NEP activity in N2a/APP695 cells
- PMID: 34316383
- PMCID: PMC8294110
- DOI: 10.1515/tnsci-2020-0178
Tripchlorolide attenuates β-amyloid generation by inducing NEP activity in N2a/APP695 cells
Abstract
Background and purpose: Alzheimer's disease (AD) is a neurodegeneration disease. The previous work from our research group demonstrated the neuroprotective effects of tripchlorolide (T4) in AD animal models.
Materials and methods: Neprilysin (NEP) is known as an important physiological amyloid-β protein (Aβ) peptide-degrading enzyme in the brain due to its apparent rate-limiting function. In this study, we explored the effect of NEP on AD model N2a/APP695 cells. Western blots and enzyme-linked immunosorbent assays were performed to assess the expression of proteins, while quantitative real-time polymerase chain reaction assays were used to evaluate RNA levels. Cell vitality was detected by the MTT assay, and reactive oxygen species (ROS) levels were assessed using a ROS activity assay kit.
Results: We discovered that T4 was able to enhance the enzyme activity of NEP. T4 administration decreased the protein levels of the soluble amyloid precursor protein. In further experiments, we found that by using thiorphan the secretion of Aβ, oxidative stress, nitrosative stress, and inflammatory factors, which were suppressed by T4, were reversed. Due to its ability to attenuate Aβ generation and to protect neurons against the neurotoxicity of Aβ, T4 may be a potential therapy in the regulation of Aβ-related pathology in AD by affecting NEP activity.
Conclusion: Tripchlorolide attenuates Aβ generation by inducing NEP activity in N2a/APP695 cells.
Keywords: amyloid-β protein, N2a/APP695 cells; neprilysin; tripchlorolide.
© 2021 Yuqi Zeng et al., published by De Gruyter.
Conflict of interest statement
Conflict of interest: The authors state no conflict of interest.
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