AUTHOR=Mossiah Isiah , Perez Sabrina M. , Stanley Taylor R. , Foley Michaela K. , Kim Guisbert Karen S. , Guisbert Eric TITLE=Geranylgeranylacetone Ameliorates Beta-Amyloid Toxicity and Extends Lifespan via the Heat Shock Response in Caenorhabditis elegans JOURNAL=Frontiers in Aging VOLUME=3 YEAR=2022 URL=https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2022.846977 DOI=10.3389/fragi.2022.846977 ISSN=2673-6217 ABSTRACT=

Activation of a cytoprotective cellular pathway known as the heat shock response (HSR) is a promising strategy for the treatment of Alzheimer’s disease and other neurodegenerative diseases. Geranylgeranylacetone (GGA) is a commonly used anti-ulcer drug in Japan that has been shown to activate the HSR. Here, we establish C. elegans as a model system to investigate the effects of GGA. First, we show that GGA-mediated activation of the HSR is conserved in worms. Then, we show that GGA can ameliorate beta-amyloid toxicity in both muscle and neuronal worm Alzheimer’s disease models. Finally, we find that exposure to GGA is sufficient to extend the lifespan of wild-type worms. Significantly, the beneficial effects of GGA on both beta-amyloid toxicity and lifespan are dependent on HSR activation. Taken together, this research supports further development of GGA as a therapeutic for Alzheimer’s disease, provides evidence that HSR activation is a relevant therapeutic mechanism, and indicates that the beneficial effects of GGA are not limited to disease.