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Spinosin Inhibits Aβ1-42 Production and Aggregation via Activating Nrf2/HO-1 Pathway
- Source :
- Biomolecules & Therapeutics. 28:259-266
- Publication Year :
- 2020
- Publisher :
- The Korean Society of Applied Pharmacology, 2020.
-
Abstract
- The present research work primarily investigated whether spinosin has the potential of improving the pathogenesis of Alzheimer’s disease (AD) driven by β-amyloid (Aβ) overproduction through impacting the procession of amyloid precursor protein (APP). Wild type mouse Neuro-2a cells (N2a/WT) and N2a stably expressing human APP695 (N2a/APP695) cells were treated with spinosin for 24 h. The levels of APP protein and secreted enzymes closely related to APP procession were examined by western blot analysis. Oxidative stress related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were detected by immunofluorescence assay and western blot analysis, respectively. The intracellular reactive oxygen species (ROS) level was analyzed by flow cytometry, the levels of Aβ1-42 were determined by ELISA kit, and Thioflavin T (ThT) assay was used to detect the effect of spinosin on Aβ1-42 aggregation. The results showed that ROS induced the expression of ADAM10 and reduced the expression of BACE1, while spinosin inhibited ROS production by activating Nrf2 and up-regulating the expression of HO-1. Additionally, spinosin reduced Aβ1-42 production by impacting the procession of APP. In addition, spinosin inhibited the aggregation of Aβ1-42. In conclusion, spinosin reduced Aβ1-42 production by activating the Nrf2/HO-1 pathway in N2a/WT and N2a/ APP695 cells. Therefore, spinosin is expected to be a promising treatment of AD.
- Subjects :
- 0301 basic medicine
ADAM10
medicine.disease_cause
Biochemistry
Neuroprotection
Flow cytometry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Western blot
Drug Discovery
medicine
Amyloid precursor protein
Heme
Pharmacology
chemistry.chemical_classification
medicine.diagnostic_test
biology
Molecular biology
030104 developmental biology
Enzyme
chemistry
030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
Oxidative stress
Subjects
Details
- ISSN :
- 20054483 and 19769148
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Biomolecules & Therapeutics
- Accession number :
- edsair.doi...........18f12011f5c7bc3f15db96a8c0bbab4d