{"doi":"10.1126/sciadv.adj4457","title":"TDP-43 impairs sleep in <i>Drosophila</i> through <i>Ataxin-2</i> –dependent metabolic disturbance","abstract":"Neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia are associated with substantial sleep disruption, which may accelerate cognitive decline and brain degeneration. Here, we define a role for trans-activation response element (TAR) DNA binding protein 43 (TDP-43), a protein associated with human neurodegenerative disease, in regulating sleep using Drosophila . Expression of TDP-43 severely disrupts sleep, and the sleep deficit is rescued by Atx2 knockdown. Brain RNA sequencing revealed that Atx2 RNA interference regulates transcripts enriched for small-molecule metabolic signaling in TDP-43 brains. Focusing on these Atx2 -regulated genes, we identified suppressors of the TDP-43 sleep phenotype enriched for metabolism pathways. Knockdown of Atx2 or treatment with rapamycin attenuated the sleep phenotype and mitigated the disruption of small-molecule glycogen metabolism caused by TDP-43. Our findings provide a connection between toxicity of TDP-43 and sleep disturbances and highlight key aspects of metabolism that interplay with TDP-43 toxicity upon Atx2 rescue.","journal":"Science Advances","year":2024,"id":431845,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"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":681382,"name":"Jaclyn Durkin","orcid":"0000-0002-0618-626X","position":1,"is_corresponding":false},{"id":681377,"name":"Samuel J. Belfer","orcid":"0000-0002-8018-879X","position":2,"is_corresponding":false},{"id":1101157,"name":"Anyara Rodriguez","orcid":"0000-0001-6071-8450","position":3,"is_corresponding":false},{"id":749440,"name":"Oksana Shcherbakova","orcid":"0000-0001-7940-3256","position":4,"is_corresponding":false},{"id":272098,"name":"Kristen Park","orcid":"0000-0002-7496-772X","position":5,"is_corresponding":false},{"id":910980,"name":"Ngoc Bao Hang Luong","orcid":"0000-0001-8983-7293","position":6,"is_corresponding":false},{"id":345521,"name":"Nancy M. Bonini","orcid":"0000-0003-0226-5291","position":7,"is_corresponding":false},{"id":394423,"name":"Matthew S. Kayser","orcid":"0000-0003-2359-4967","position":8,"is_corresponding":false},{"id":749441,"name":"Alexandra E. Perlegos","orcid":"0000-0002-4243-7644","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T01:59:30.747263Z","pmid":"38198547","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":[]}