@article{f5946a801d0049aabc4316db78bad7d9,
title = "Sir-2.1 mediated attenuation of α-synuclein expression by Alaskan bog blueberry polyphenols in a transgenic model of Caenorhabditis elegans",
abstract = "Misfolding and accumulation of cellular protein aggregates are pathological hallmarks of aging and neurodegeneration. One such protein is α-synuclein, which when misfolded, forms aggregates and disrupts normal cellular functions of the neurons causing Parkinson{\textquoteright}s disease. Nutritional interventions abundant in pharmacologically potent polyphenols have demonstrated a therapeutic role for combating protein aggregation associated with neurodegeneration. The current study hypothesized that Alaskan bog blueberry (Vaccinum uliginosum), which is high in polyphenolic content, will reduce α-synuclein expression in a model of Caenorhabditis elegans (C. elegans). We observed that blueberry extracts attenuated α-synuclein protein expression, improved healthspan in the form of motility and restored lipid content in the transgenic strain of C. elegans expressing human α-synuclein. We also found reduced gene expression levels of sir-2.1 (ortholog of mammalian Sirtuin 1) in blueberry treated transgenic animals indicating that the beneficial effects of blueberries could be mediated through partial reduction of sirtuin activity. This therapeutic effect of the blueberries was attributed to its xenohormetic properties. The current results highlight the role of Alaskan blueberries in mediating inhibition of sir-2.1 as a novel therapeutic approach to improving pathologies of protein misfolding diseases. Finally, our study warrants further investigation of the structure, and specificity of such small molecules from indigenous natural compounds and its role as sirtuin regulators.",
author = "Malabika Maulik and Swarup Mitra and Skyler Hunter and Moriah Hunstiger and Oliver, {S. Ryan} and Abel Bult-Ito and Taylor, {Barbara E.}",
note = "Funding Information: The authors thank Dr. Mitchell Reed, Ian Herriott and Noah Khalsa for their support with the experiments and Dr. Jennifer Guerard and Kristen Gagne for the blueberry extractions. We would also like to thank Drs. Thomas Kuhn and Elena Vayndorf for their intellectual contributions. The strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Research reported in this publication was funded by grants from the National Institute of General Medical Sciences of the National Institutes of Health (1) under an Institutional Development Award (IDeA; grant number P20GM103395) and (2) under a Building Infrastructure Leading to Diversity Award (BUILD; three linked grants numbered RL5GM118990, TL4GM118992, and 1UL1GM118991). The work is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health. UA is an AA/EO employer and educational institution and prohibits illegal discrimination against any individual: www.alaska.edu/ titleIXcompliance/nondiscrimination. The authors also thank the Office of the Vice Chancellor of Research, Dr. Larry Hinzman, with the funding associated with the publication costs of this article. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41598-018-26905-4",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}