title: Cranberry Extract Standardized for Proanthocyanidins Alleviates β-Amyloid Peptide Toxicity by Improving Proteostasis Through HSF-1 in Caenorhabditis elegans Model of Alzheimer's Disease.
abstract: A growing body of evidence suggests that nutraceuticals with prolongevity properties may delay the onset of Alzheimer's disease (AD). We recently demonstrated that a proanthocyanidins-standardized cranberry extract has properties that prolong life span and promote innate immunity in Caenorhabditis elegans In this article, we report that supplementation of this cranberry extract delayed Aβ toxicity-triggered body paralysis in the C elegans AD model. Genetic analyses indicated that the cranberry-mediated Aβ toxicity alleviation required heat shock transcription factor (HSF)-1 rather than DAF-16 and SKN-1. Moreover, cranberry supplementation increased the transactivity of HSF-1 in an IIS-dependent manner. Further studies found that the cranberry extract relies on HSF-1 to significantly enhance the solubility of proteins in aged worms, implying an improved proteostasis in AD worms. Considering that HSF-1 plays a pivotal role in maintaining proteostasis, our results suggest that cranberry maintains the function of proteostasis through HSF-1, thereby protecting C elegans against Aβ toxicity. Together, our findings elucidated the mechanism whereby cranberry attenuated Aβ toxicity in C elegans and stressed the significance of proteostasis in the prevention of age-related diseases from a practical point of view.
authors.affiliation: Department of Biological Sciences, Clemson University, South Carolina.|School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Biological Sciences, Clemson University, South Carolina.|Institute for Engaged Aging, Clemson University, Clemson, South Carolina.
authors.forename: Min
authors.initials: M
authors.lastname: Cao
authors.affiliation: Functional Genomics Unit, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
authors.forename: Sige
authors.initials: S
authors.lastname: Zou
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Boping
authors.initials: B
authors.lastname: Ye
authors.affiliation: Department of Biological Sciences, Clemson University, South Carolina. ydong@clemson.edu.|Institute for Engaged Aging, Clemson University, Clemson, South Carolina.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000375:Aging / Q000187:drug effects*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000187:drug effects*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000187:drug effects; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors; D000076249:Heat Shock Transcription Factors; D007113:Immunity, Innate; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000737:chemistry / Q000494:pharmacology*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000187:drug effects; D029799:Vaccinium macrocarpon
chemical_list: D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D000076249:Heat Shock Transcription Factors; D010936:Plant Extracts; D044945:Proanthocyanidins; D020011:Protective Agents; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans; C073702:skn-1 protein, C elegans
keywords: 
  Caenorhabditis elegans
  ; 
  hsf-1
  ; Alzheimer’s disease; Cranberry; Proteostasis; β-Amyloid