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- W3037112179 abstract "ABSTRACT Background Alzheimer’s disease (AD) has challenged single-target therapeutic strategies, raising the possibility that combined therapies may offer a more effective treatment strategy. Objective There is substantial evidence for the efficacy of leptin (L) (neuroprotective hormone) and pioglitazone (P) (anti-inflammatory agent) as monotherapies in AD. We have previouly shown that combination treatment of L+P in APP/PS1 mice at the onset of pathology significantly improved memory and reduced brain Aβ levels relative to control mice. In this new study, we sought to replicate our previous findings in a new cohort of APP/PS1 mouse to further confirm whether the combined treatment of L+P is superior to each treatment individually. Methods We have re-evaluated the effects of L+P co-treatment in APP/PS1 mice using thioflavin-S staining, MOAβ immunolabeling and enzyme-linked immunosorbent assay (ELISA) to examine effects on Aβ levels and pathology, relative to animals that received L or P individually. To explore mechanism of regulation, we used Western blotting to examine the expression of the peroxisome-proliferator activated receptor γ (PPARγ), due to its potential role in the regulation of the inflammatory response. Results We demonstrated that combining L and P significantly enhances the anti-Aβ effect of L or P in the hippocampus of APP/PS1 mice. Western blot analysis indicated that Aβ reduction was accompanied by up-regulation of the PPARγ levels. Conclusion Our findings suggest that combining L and P significantly enhances the anti-Aβ effect of L or P in the hippocampus of APP/PS1 mice, and may be a potential new effective strategy for AD therapy." @default.
- W3037112179 created "2020-07-02" @default.
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- W3037112179 date "2020-06-24" @default.
- W3037112179 modified "2023-10-18" @default.
- W3037112179 title "Enhanced anti-amyloid effect of combined leptin and pioglitazone in APP/PS1 transgenic mice" @default.
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- W3037112179 doi "https://doi.org/10.1101/2020.06.24.168518" @default.
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