title: Neuroprotective effects of Wnt/β-catenin signaling pathway against Aβ -induced tau protein over-phosphorylation in PC12 cells.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease, which is characterized by deposition of senile plaque (SP) and appearance of neurofibrillary tangles (NFT) in the cerebral cortex and hippocampus. SP is the accumulation of extracellular proteins/peptides, mainly consisting of the amyloid-beta protein (Aβ), and the atrophy-degraded neuritis, microglias and astrocytes. NFT could be induced by the abnormal phosphorylation of Tau protein. Aβ may interfere with certain cell signal systems, which affects the level of Tau protein phosphorylation thus resulting in the forming of NFT. The present study explored the role of Wnt/β-catenin pathway in the neurotoxic effect of Aβ25-35 on PC12 cells. Flow cytometry was employed to determine the effective sublethally dose of Aβ25-35, immunocytochemistry to decipher the intracellular distribution of microtubule associated protein-2 (MAP-2) and neurofilament H (NF-H), western blotting to assess the protein abundance of phosphorylated tau in several sites and GSK-3. As a result, the Polymerization of and MAP-2 and NF-H induced by Aβ25-35 could be significantly inhibited by Wnt3a(40 ng/ml), however enhanced by Dkk1(100 ng/ml). Meanwhile, the protein abundance of phosphorylated tau in several sites is decreased by Wnt3a, but increased by Dkk1 significantly compared with the control group. In conclusion, Wnt/β-catenin signaling pathway is involved in the neurotoxic effect of Aβ25-35 on PC12 cells.
authors.affiliation: LuoHe Medical College, Henan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology, Medical College of Zhengzhou University, Zhengzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jing
authors.affiliation: The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Physiology, Medical College of Zhengzhou University, Zhengzhou, China. Electronic address: 17655507933@gmail.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xing
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D000066829:Neuroprotection; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D010766:Phosphorylation; D051381:Rats; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000378:metabolism / Q000494:pharmacology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C531384:Dkk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; C489131:Mapt protein, rat; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D060509:Wnt3A Protein; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; C051774:neurofilament protein H
keywords: Aβ(25-35); PC12 cell; Wnt signaling pathway