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Cranberry Extract Standardized for Proanthocyanidins Alleviates β-Amyloid Peptide Toxicity by Improving Proteostasis Through HSF-1 in Caenorhabditis elegans Model of Alzheimer's Disease.
J Gerontol A Biol Sci Med Sci. 2016 12; 71(12):1564-1573.JG

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+Show Affiliations

Department of Biological Sciences, Clemson University, South Carolina. School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.Department of Biological Sciences, Clemson University, South Carolina. Institute for Engaged Aging, Clemson University, Clemson, South Carolina.Functional Genomics Unit, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.Department of Biological Sciences, Clemson University, South Carolina. ydong@clemson.edu. Institute for Engaged Aging, Clemson University, Clemson, South Carolina.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

26405062

Citation

Guo, Hong, et al. "Cranberry Extract Standardized for Proanthocyanidins Alleviates β-Amyloid Peptide Toxicity By Improving Proteostasis Through HSF-1 in Caenorhabditis Elegans Model of Alzheimer's Disease." The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, vol. 71, no. 12, 2016, pp. 1564-1573.
Guo H, Cao M, Zou S, et al. Cranberry Extract Standardized for Proanthocyanidins Alleviates β-Amyloid Peptide Toxicity by Improving Proteostasis Through HSF-1 in Caenorhabditis elegans Model of Alzheimer's Disease. J Gerontol A Biol Sci Med Sci. 2016;71(12):1564-1573.
Guo, H., Cao, M., Zou, S., Ye, B., & Dong, Y. (2016). Cranberry Extract Standardized for Proanthocyanidins Alleviates β-Amyloid Peptide Toxicity by Improving Proteostasis Through HSF-1 in Caenorhabditis elegans Model of Alzheimer's Disease. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 71(12), 1564-1573.
Guo H, et al. Cranberry Extract Standardized for Proanthocyanidins Alleviates β-Amyloid Peptide Toxicity By Improving Proteostasis Through HSF-1 in Caenorhabditis Elegans Model of Alzheimer's Disease. J Gerontol A Biol Sci Med Sci. 2016;71(12):1564-1573. PubMed PMID: 26405062.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cranberry Extract Standardized for Proanthocyanidins Alleviates β-Amyloid Peptide Toxicity by Improving Proteostasis Through HSF-1 in Caenorhabditis elegans Model of Alzheimer's Disease. AU - Guo,Hong, AU - Cao,Min, AU - Zou,Sige, AU - Ye,Boping, AU - Dong,Yuqing, Y1 - 2015/09/23/ PY - 2015/01/16/received PY - 2015/08/31/accepted PY - 2015/9/26/pubmed PY - 2017/7/25/medline PY - 2015/9/26/entrez KW - Caenorhabditis elegans KW - hsf-1 KW - Alzheimer’s disease KW - Cranberry KW - Proteostasis KW - β-Amyloid SP - 1564 EP - 1573 JF - The journals of gerontology. Series A, Biological sciences and medical sciences JO - J. Gerontol. A Biol. Sci. Med. Sci. VL - 71 IS - 12 N2 - 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. SN - 1758-535X UR - https://www.unboundmedicine.com/medline/citation/26405062/Cranberry_Extract_Standardized_for_Proanthocyanidins_Alleviates_β_Amyloid_Peptide_Toxicity_by_Improving_Proteostasis_Through_HSF_1_in_Caenorhabditis_elegans_Model_of_Alzheimer's_Disease_ L2 - https://academic.oup.com/biomedgerontology/article-lookup/doi/10.1093/gerona/glv165 DB - PRIME DP - Unbound Medicine ER -