{"doi":"10.3389/fragi.2022.846977","title":"Geranylgeranylacetone Ameliorates Beta-Amyloid Toxicity and Extends Lifespan via the Heat Shock Response in Caenorhabditis elegans","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.","journal":"Frontiers in Aging","year":2022,"id":286504,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":933688,"name":"Sabrina M. Perez","orcid":"0000-0002-0246-4699","position":1,"is_corresponding":false},{"id":934340,"name":"Taylor R. Stanley","orcid":null,"position":2,"is_corresponding":false},{"id":941341,"name":"Michaela K. Foley","orcid":"0000-0002-2534-1974","position":3,"is_corresponding":false},{"id":426597,"name":"Karen S. Kim Guisbert","orcid":"0000-0001-9907-9502","position":4,"is_corresponding":false},{"id":426598,"name":"Eric Guisbert","orcid":"0000-0003-1901-5598","position":5,"is_corresponding":false},{"id":721486,"name":"Isiah Mossiah","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T00:29:52.825777Z","pmid":"35821801","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}