title: 18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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. Antioxid. Redox Signal. 25, 855-869.
authors.affiliation: 1 Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation , Athens, Greece .|2 Faculty of Biology and Pharmacy, Institute of Nutrition, Friedrich Schiller University of Jena , Jena, Germany .
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Papaevgeniou
authors.affiliation: 1 Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation , Athens, Greece .|3 Medical School, Örebro University , Örebro, Sweden .
authors.forename: Marianthi
authors.initials: M
authors.lastname: Sakellari
authors.affiliation: 4 Translational Cancer Biology Program, Research Programs Unit, University of Helsinki , Helsinki, Finland .
authors.forename: Sweta
authors.initials: S
authors.lastname: Jha
authors.affiliation: 5 Institute of Molecular Biology and Biotechnology , Foundation for Research and Technology-Hellas, Heraklion, Greece .|6 Faculty of Medicine, Department of Basic Sciences, University of Crete , Heraklion, Greece .
authors.forename: Nektarios
authors.initials: N
authors.lastname: Tavernarakis
authors.affiliation: 4 Translational Cancer Biology Program, Research Programs Unit, University of Helsinki , Helsinki, Finland .
authors.forename: Carina I
authors.initials: CI
authors.lastname: Holmberg
authors.affiliation: 1 Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation , Athens, Greece .|3 Medical School, Örebro University , Örebro, Sweden .
authors.forename: Efstathios S
authors.initials: ES
authors.lastname: Gonos
authors.affiliation: 1 Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation , Athens, Greece .
authors.forename: Niki
authors.initials: N
authors.lastname: Chondrogianni
mesh_terms: D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D018450:Disease Progression; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008136:Longevity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; C119129:18alpha-glycyrrhetinic acid; D046988:Proteasome Endopeptidase Complex; D006034:Glycyrrhetinic Acid
keywords: Alzheimer's disease; aggregation; aging; lifespan extension; proteasome activation; proteostasis