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Oncotarget. 2016 Oct 18;7(42):67716-67731. doi: 10.18632/oncotarget.11963.

Quercetin ameliorates Aβ toxicity in Drosophila AD model by modulating cell cycle-related protein expression.

Author information

1
Department of Biochemistry and Molecular Biology, Medical School, Southeast University, Nanjing, Jiangsu, China.
2
Gladstone Institute of Cardiovascular Disease and Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
3
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
4
State Education Ministry's Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University, China.

Abstract

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by β amyloid (Aβ) deposition and neurofibril tangles. It has been reported that a bioflavonoid, quercetin, could ameliorate AD phenotypes in C. elegans and mice. However, the mechanism underlying the ameliorative effect of quercetin is not fully understood yet. Drosophila models could recapitulate AD-like phenotypes, such as shortened lifespan, impaired locomotive ability as well as defects in learning and memory. So in this study, we investigated the effects of quercetin on AD in Drosophila model and explored the underlying mechanisms. We found quercetin could effectively intervene in AD pathogenesis in vivo. Mechanism study showed quercetin could restore the expression of genes perturbed by Aβ accumulation, such as those involved in cell cycle and DNA replication. Cyclin B, an important cell cycle protein, was chosen to test whether it participated in the AD ameliorative effects of quercetin. We found that cyclin B RNAi in the brain could alleviate AD phenotypes. Taken together, the current study suggested that the neuroprotective effects of quercetin were mediated at least partially by targeting cell cycle-related proteins.

KEYWORDS:

Alzheimer’s disease; DNA replication; Drosophila; cell cycle; quercetin; Gerotarget

PMID:
27626494
PMCID:
PMC5356514
DOI:
10.18632/oncotarget.11963
[Indexed for MEDLINE]
Free PMC Article

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