{"doi":"10.1101/2024.04.09.588761","title":"Loss of age-accumulated <i>crh-1</i> circRNAs ameliorate amyloid β-induced toxicity in a <i>C. elegans</i> model for Alzheimer’s disease","abstract":"ABSTRACT Circular RNAs (circRNAs) are non-coding RNAs mostly derived from exons of protein-coding genes via a back-splicing process. The expression of hundreds of circRNAs accumulates during healthy aging and is associated with Alzheimer’s disease (AD), characterized by the accumulation of amyloid-beta (Aβ) proteins. In C. elegans , many circRNAs were previously found to accumulate during aging, with loss of age-accumulated circRNAs derived from the CREB gene (circ- crh-1 ) to increase mean lifespan. Here, we used C. elegans to study the effects of age-accumulated circRNAs on the age-related onset of Aβ-toxicity. We found that circ- crh-1 mutations delayed Aβ-induced muscle paralysis and lifespan phenotypes in a transgenic C. elegans strain expressing a full-length human Aβ-peptide (Aβ 1-42 ) selectively in muscle cells (GMC101). The delayed Aβ phenotypic defects were associated with inhibiting the deposition of Aβ aggregates, and thus, genetic removal of circ- crh-1 provides protection against Aβ-induced toxicity. Consistent with a detrimental role for age-accumulated circRNAs in AD, circ- crh-1 expression level is elevated after induction of Aβ during aging, whereas linear crh-1 mRNA expression remains unchanged. Finally, we show that a circ- crh-1 upregulated collagen gene, col-49 , promotes Aβ-induced paralysis. Taken together, our results show that the loss of an age-accumulated circRNA exerts a protective role on Aβ-induced toxicity, demonstrating the utility of C. elegans for studying circRNAs in AD and its relationship to aging.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490658,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9479,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1336216,"name":"Thomas Ballinger","orcid":null,"position":1,"is_corresponding":false},{"id":1336217,"name":"Everett Rojas","orcid":null,"position":2,"is_corresponding":false},{"id":343772,"name":"Alexander M. van der Linden","orcid":"0000-0002-4870-7684","position":3,"is_corresponding":false},{"id":1335916,"name":"Hussam Z. Alshareef","orcid":"0000-0003-4980-3456","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:08:37.162700Z","pmid":null,"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":[]}