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

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Papaevgeniou , N , Sakellari , M , Jha , S , Tavernarakis , N , Holmberg , C I , Gonos , E S & Chondrogianni , N 2016 , ' 18 alpha-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures ' , Antioxidants & Redox Signaling , vol. 25 , no. 16 , pp. 855-869 . https://doi.org/10.1089/ars.2015.6494

Title: 18 alpha-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures
Author: Papaevgeniou, Nikoletta; Sakellari, Marianthi; Jha, Sweta; Tavernarakis, Nektarios; Holmberg, Carina I.; Gonos, Efstathios S.; Chondrogianni, Niki
Contributor: University of Helsinki, Research Programs Unit
Date: 2016-12-01
Language: eng
Number of pages: 15
Belongs to series: Antioxidants & Redox Signaling
ISSN: 1523-0864
URI: http://hdl.handle.net/10138/172346
Abstract: 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 18 alpha-glycyrrhetinic acid (18 alpha-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasomeactivation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased A beta 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 18 alpha-GA treatment. Innovation: This is the first report of the use of 18 alpha-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: proteasome activation
lifespan extension
aging
Alzheimer's disease
aggregation
proteostasis
TRANSCRIPTION FACTOR SKN-1
CELLULAR STRESS RESPONSES
LIFE-SPAN EXTENSION
OXIDATIVE-STRESS
HUMAN FIBROBLASTS
C. ELEGANS
IN-VITRO
LONGEVITY
RESISTANCE
PROTEIN
3111 Biomedicine
3112 Neurosciences
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