{"doi":"10.1016/j.nbd.2020.105078","title":"Optogenetic TDP-43 nucleation induces persistent insoluble species and progressive motor dysfunction in vivo","abstract":"TDP-43 is a predominantly nuclear DNA/RNA binding protein that is often mislocalized into insoluble cytoplasmic inclusions in post-mortem patient tissue in a variety of neurodegenerative disorders including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). The underlying causes of TDP-43 proteinopathies remain unclear, but recent studies indicate the formation of these protein assemblies is driven by aberrant phase transitions of RNA deficient TDP-43. Technical limitations have prevented our ability to understand how TDP-43 proteinopathy relates to disease pathogenesis. Current animal models of TDP-43 proteinopathy often rely on overexpression of wild-type TDP-43 to non-physiological levels that may initiate neurotoxicity through nuclear gain of function mechanisms, or by the expression of disease-causing mutations found in only a fraction of ALS patients. New technologies allowing for light-responsive control of subcellular protein crowding provide a promising approach to drive intracellular protein aggregation, as we have previously demonstrated in vitro. Here we present a model for the optogenetic induction of TDP-43 proteinopathy in Drosophila that recapitulates key features of patient pathology, including detergent insoluble cytoplamsic inclusions and progressive motor dysfunction.","journal":"Neurobiology of Disease","year":2020,"id":103424,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9471,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":503620,"name":"Tyler R. Fortuna","orcid":"0000-0003-0744-9532","position":1,"is_corresponding":false},{"id":501164,"name":"Jacob R. Mann","orcid":"0000-0003-2553-6015","position":2,"is_corresponding":false},{"id":501163,"name":"Amanda M. Gleixner","orcid":"0000-0001-8241-8408","position":3,"is_corresponding":false},{"id":350455,"name":"Nandini Ramesh","orcid":"0000-0003-0860-2922","position":4,"is_corresponding":false},{"id":124526,"name":"Noah J. Pyles","orcid":null,"position":5,"is_corresponding":false},{"id":350458,"name":"Udai Bhan Pandey","orcid":"0000-0002-6267-0179","position":6,"is_corresponding":false},{"id":501165,"name":"Christopher J. Donnelly","orcid":"0000-0002-2383-9015","position":7,"is_corresponding":false},{"id":504168,"name":"Charlton G. Otte","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:42:17.920911Z","pmid":"32927062","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":[]}