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Quercetin inhibits okadaic acid-induced tau protein hyperphosphorylation through the Ca2+‑calpain‑p25‑CDK5 pathway in HT22 cells
- Source :
- International Journal of Molecular Medicine.
- Publication Year :
- 2017
- Publisher :
- Spandidos Publications, 2017.
-
Abstract
- Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by aberrant tau protein hyperphosphorylation, which eventually leads to the formation of neurofibrillary tangles. Hyperphosphorylated tau protein is considered as a vital factor in the development of AD and is highly associated with cognitive impairment. Therefore, it is recognized to be a potential therapeutic target. Quercetin (QUE) is a naturally occurring flavonoid compound. In the present study, the inhibitory effect of QUE on okadaic acid (OA)-induced tau protein hyperphosphorylation in HT22 cells was explored. Western blotting results indicated that QUE significantly attenuated OA‑induced tau protein hyperphosphorylation at the Ser396, Ser199, Thr231 and Thr205 sites. Further experiments demonstrated that QUE inhibited the activity of cyclin‑dependent kinase 5 (CDK5), a key enzyme in the regulation of tau protein, and blocked the Ca2+‑calpain‑p25‑CDK5 signaling pathway. These observations indicate the ability of QUE to decrease tau protein hyperphosphorylation and thereby attenuate the associated neuropathology. In conclusion, these results support the potential of QUE as a therapeutic agent for AD and other neurodegenerative tauopathies.
- Subjects :
- 0301 basic medicine
Tau protein
Hyperphosphorylation
Nerve Tissue Proteins
tau Proteins
Hippocampus
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Alzheimer Disease
Okadaic Acid
Genetics
medicine
Humans
Cognitive Dysfunction
Phosphorylation
Neurons
biology
Calpain
Chemistry
Cyclin-dependent kinase 5
Cyclin-Dependent Kinase 5
General Medicine
Okadaic acid
medicine.disease
Cell biology
030104 developmental biology
biology.protein
Calcium
Quercetin
Alzheimer's disease
Signal transduction
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 1791244X and 11073756
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Medicine
- Accession number :
- edsair.doi.dedup.....e4ac027d06f2200757d178154181eaf3