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?:abstract
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BACKGROUND: It has been demonstrated IKKß facilitates autophagy, which in turn mediates p-Tau protein clearance. However, the specific regulatory mechanism in AD remains unclear. METHODS: Firstly, AD model was generated by the intracerebroventricular (ICV) injection of the Aß1-42 peptide. Subsequently, mice were injected with shRNA adenoviral transduction particles designed to target DJ-1 or Aß1-42 or Aß1-42+shNC or Aß1-42+shRNA against DJ-1. shRNA against DJ-1 were injected into hippocampus of mice (8×104 viral particles for each mice) for 7 consecutive days. Immunohistochemistry was performed to detect the accumulation of Aß in the hippocampus of mice, and HE staining assay was carried to detect pathological changes in the hippocampus of mice. Further, sh-IKKß, shDJ-1, pcDNA-IKKß and pcDNA-DJ-1 plasmids were transfected into HT-22 cells, MTT assay, TUNEL staining and Hoechst staining were performed to detect cell viability and apoptosis, respectively. Western blotting was carried to measure the relative proteins expression. RESULTS: Findings indicated that Aß1-42 inhibited autophagy and up-regulated p-Tau protein expression; the overexpression of IKKß and DJ-1 all rescued the autophagy inhibited by Aß1-42 and down-regulated p-Tau protein expression induced by Aß1-42; DJ-1 up-regulated IKKß via p-VHL, further promoted autophagy and reduced the expression of p-Tau protein; DJ-1 knockdown inhibited autophagy and up-regulated p-Tau protein expression, resulting in delayed behavior in mice. CONCLUSION: In conclusion, IKKß, modulated by DJ-1p-VHL, reduces p-Tau accumulation via autophagy in AD\'s disease model. This study may provide theoretical basis for the treatment of AD.
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