Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions

Abstract Oxidative stress is damaging to cells and contributes to aging and neurodegenerative disease. This state is mediated by production of imbalanced molecules, and reactive dicarbonyl compounds - mainly methylglyoxal. The glyoxalase pathway is an antioxidant defense system utilized to detoxify...

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Autores principales:	Joel Frandsen, Prabagaran Narayanasamy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d301b8c313646898b9c429cb8f14023
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spelling	oai:doaj.org-article:1d301b8c313646898b9c429cb8f140232021-12-02T16:06:31ZFlavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions10.1038/s41598-017-05287-z2045-2322https://doaj.org/article/1d301b8c313646898b9c429cb8f140232017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05287-zhttps://doaj.org/toc/2045-2322Abstract Oxidative stress is damaging to cells and contributes to aging and neurodegenerative disease. This state is mediated by production of imbalanced molecules, and reactive dicarbonyl compounds - mainly methylglyoxal. The glyoxalase pathway is an antioxidant defense system utilized to detoxify methylglyoxal and neutralize free radicals. Pathway dysfunction leads to overproduction and accumulation of toxic, prooxidant compounds. We hypothesize flavonoid treatment as a means to enhance the glyoxalase pathway’s ability to detoxify in neurons. This study found that flavonoid treatment in methylglyoxal treated cerebellar neurons increased the functioning of glyoxalase pathway by enhancing expression of glyoxalase-1 and glyoxalase-2 proteins, decreased cell death and increased cellular viability. Flavonoids also significantly contributed in the retention of synaptic functions (VGLUT1 and GAD65) in cerebellar neurons. In addition, flavonoids were found to be involved in pAkt - NF-κB signaling pathway through a reduction in phosphorylation of Akt. The data here show flavonoid compounds have the potential to protect the brain from aging and neurodegenerative disease.Joel FrandsenPrabagaran NarayanasamyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joel Frandsen Prabagaran Narayanasamy Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions
description	Abstract Oxidative stress is damaging to cells and contributes to aging and neurodegenerative disease. This state is mediated by production of imbalanced molecules, and reactive dicarbonyl compounds - mainly methylglyoxal. The glyoxalase pathway is an antioxidant defense system utilized to detoxify methylglyoxal and neutralize free radicals. Pathway dysfunction leads to overproduction and accumulation of toxic, prooxidant compounds. We hypothesize flavonoid treatment as a means to enhance the glyoxalase pathway’s ability to detoxify in neurons. This study found that flavonoid treatment in methylglyoxal treated cerebellar neurons increased the functioning of glyoxalase pathway by enhancing expression of glyoxalase-1 and glyoxalase-2 proteins, decreased cell death and increased cellular viability. Flavonoids also significantly contributed in the retention of synaptic functions (VGLUT1 and GAD65) in cerebellar neurons. In addition, flavonoids were found to be involved in pAkt - NF-κB signaling pathway through a reduction in phosphorylation of Akt. The data here show flavonoid compounds have the potential to protect the brain from aging and neurodegenerative disease.
format	article
author	Joel Frandsen Prabagaran Narayanasamy
author_facet	Joel Frandsen Prabagaran Narayanasamy
author_sort	Joel Frandsen
title	Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions
title_short	Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions
title_full	Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions
title_fullStr	Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions
title_full_unstemmed	Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions
title_sort	flavonoid enhances the glyoxalase pathway in cerebellar neurons to retain cellular functions
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1d301b8c313646898b9c429cb8f14023
work_keys_str_mv	AT joelfrandsen flavonoidenhancestheglyoxalasepathwayincerebellarneuronstoretaincellularfunctions AT prabagarannarayanasamy flavonoidenhancestheglyoxalasepathwayincerebellarneuronstoretaincellularfunctions
_version_	1718384950147809280

Flavonoid Enhances the Glyoxalase Pathway in Cerebellar Neurons to Retain Cellular Functions

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