18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures

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18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures

Papaevgeniou, Nikoletta (author): Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece; Faculty of Biology and Pharmacy, Institute of Nutrition, Friedrich Schiller University of Jena, Jena, Germany

Sakellari, Marianthi, 1987- (author): Örebro universitet,Institutionen för medicinska vetenskaper,Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece

Jha, Sweta (author): Translational Cancer Biology Program, Research Programs Unit, University of Helsinki, Helsinki, Finland

Tavernarakis, Nektarios (author): Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece; Faculty of Medicine, Department of Basic Sciences, University of Crete, Heraklion, Greece

Holmberg, Carina I. (author): Programs Unit, University of Helsinki, Helsinki, Finland

Gonos, Efstathios S. (author): Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece; Medical School, Örebro University, Örebro, Sweden

Chondrogianni, Niki (author): Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece

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New Rochelle, USA : Mary Ann Liebert, 2016
2016
English.
In: Antioxidants and Redox Signaling. - New Rochelle, USA : Mary Ann Liebert. - 1523-0864 .- 1557-7716. ; 25:16, s. 855-869

Related links:: https://doi.org/10.1...; show more...; https://www.liebertp...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Aims: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression.Results: Feeding of wild-type Caenorhabditis elegans with 18α-glycyrrhetinic acid (18α-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Aβ deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18α-GA treatment.Innovation: This is the first report of the use of 18α-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism.Conclusion: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet.

Subject headings

NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Keyword

Proteasome activation
lifespan extension
aging
Alzheimer’s disease
aggregation
proteostasis

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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By the university: Örebro University

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