{"doi":"10.1073/pnas.2022115118","title":"Chemical and genetic rescue of in vivo progranulin-deficient lysosomal and autophagic defects.","abstract":"Significance Uncovering the genetic and cellular mechanisms of frontotemporal dementia (FTD) may lead to new therapeutic strategies. Mutations in the GRN gene are linked to FTD; the underlying cellular mechanisms are still unknown, but current research points to lysosomal dysfunction. Using the model organism Caenorhabditis elegans , we found a link between pgrn-1 / GRN mutations, and sphingolipid metabolism and autophagy. We further identified small molecules that attenuated several pgrn-1 / GRN phenotypes in vivo. These results offer sphingolipid metabolism as a potential mechanism contributing to FTD pathogenesis and suggest that efforts to restore sphingolipid homeostasis may be a beneficial therapeutic approach.","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":190974,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":435579,"name":"Claudia Maios","orcid":"0000-0003-2259-8835","position":1,"is_corresponding":false},{"id":364292,"name":"Céline Vrancx","orcid":"0000-0003-2594-9020","position":2,"is_corresponding":false},{"id":755820,"name":"Sarah Duhaime","orcid":"0000-0002-0397-8579","position":3,"is_corresponding":false},{"id":755821,"name":"Babykumari P. Chitramuthu","orcid":"0000-0001-5997-0915","position":4,"is_corresponding":false},{"id":755822,"name":"H.P.J. Bennett","orcid":"0000-0003-2892-1648","position":5,"is_corresponding":false},{"id":755823,"name":"Andrew Bateman","orcid":"0000-0003-0597-769X","position":6,"is_corresponding":false},{"id":435581,"name":"J. Alex Parker","orcid":"0000-0002-3333-2445","position":7,"is_corresponding":false},{"id":538466,"name":"James J Doyle","orcid":null,"position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:49:31.121780Z","pmid":"34140407","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":[]}