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2016 (English)In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 25, no 16, p. 855-869Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
New Rochelle, USA: Mary Ann Liebert, 2016
Keywords
Proteasome activation, lifespan extension, aging, Alzheimer’s disease, aggregation, proteostasis
National Category
Biochemistry Molecular Biology
Identifiers
urn:nbn:se:oru:diva-49639 (URN)10.1089/ars.2015.6494 (DOI)000388262600001 ()26886723 (PubMedID)2-s2.0-85002156990 (Scopus ID)
Note
Funding Agencies:
U.S. National Institutes of Health National Center for Research Resources
Thales GenAge QALHS AP:10479/3.7.12 MIS380228
MAESTRO by the European Union (European Social Fund)
Operational Program, Education and Lifelong Learning, of the National Strategic Reference Framework (NSRF)
European Union 266486
IKYDA fellowship
Empirikion Foundation Scientific Project
John S. Latsis Public Benefit Foundation
Academy of Finland 259797
COST Actions PROTEOS-TASIS BM1307
GENiE BM1408
COST (European Cooperation in Science and Technology)
2016-04-202016-04-052025-02-20Bibliographically approved