{"doi":"10.1101/2022.07.24.501274","title":"An intestinal sphingolipid promotes neuronal health across generations","abstract":"Abstract Maternal diet and environment can influence the neuronal health of offspring. Here, we report that diet-induced intestinal sphingolipid biosynthesis reduces adult-onset neurodegeneration intergenerationally in Caenorhabditis elegans . Feeding C. elegans with ursolic acid (UA), a natural plant product, provides neuroprotection by enhancing maternal provisioning of sphingosine-1-phosphate (S1P) - a bioactive sphingolipid. S1P promotes neuronal health across generations by upregulating transcription of the acid ceramidase-1 ( asah-1 ) gene in the intestine. Intergenerational intestine-to-oocyte S1P transfer is essential for promoting neuronal health and is dependent on the lipoprotein yolk receptor RME-2 (Receptor-Mediated Endocytosis-2). Spatially regulating sphingolipid biosynthesis is critical, as inappropriate asah-1 neuronal expression causes developmental axon outgrowth defects. Our results reveal that sphingolipid homeostasis impacts the development and intergenerational health of the nervous system. One-Sentence Summary An intestinal lipid prevents neurodegeneration across generations.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":310126,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"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":567271,"name":"Tessa Sherry","orcid":"0000-0002-8129-659X","position":1,"is_corresponding":false},{"id":426299,"name":"Xinran Cheng","orcid":"0000-0003-3543-1559","position":2,"is_corresponding":false},{"id":334657,"name":"Qi Fan","orcid":"0000-0003-3423-5601","position":3,"is_corresponding":false},{"id":880753,"name":"Rebecca Cornell","orcid":"0000-0001-7242-1283","position":4,"is_corresponding":false},{"id":1005238,"name":"Jie Liu","orcid":"0000-0002-3639-2048","position":5,"is_corresponding":false},{"id":1005239,"name":"Zhi‐Cheng Xiao","orcid":"0000-0001-5172-762X","position":6,"is_corresponding":false},{"id":567273,"name":"Roger Pocock","orcid":"0000-0002-5515-3608","position":7,"is_corresponding":false},{"id":949997,"name":"Wenyue Wang","orcid":"0009-0007-9059-6950","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:33:15.860993Z","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":[]}