{"doi":"10.1101/2024.04.03.587963","title":"Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons","abstract":"Abstract Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by re-expression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral re-expression of ISL1 and LHX3 reactivates aspects of the youthful gene expression program in mature motor neurons and alleviates key disease-relevant phenotypes in the SOD1 G93A mouse model of ALS. Our results suggest that redeployment of lineage-specific neuronal selector transcription factors can be an effective strategy to attenuate age-dependent phenotypes in neurodegenerative disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":496309,"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":0.9552,"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":683171,"name":"Tulsi Patel","orcid":"0000-0002-3635-3567","position":1,"is_corresponding":false},{"id":1343145,"name":"Jonathon A. Costa","orcid":null,"position":2,"is_corresponding":false},{"id":379327,"name":"Elizabeth Chang","orcid":"0000-0002-4439-1854","position":3,"is_corresponding":false},{"id":1343146,"name":"Shahroz Tariq","orcid":null,"position":4,"is_corresponding":false},{"id":1343147,"name":"Hranush Melikyan","orcid":null,"position":5,"is_corresponding":false},{"id":1342841,"name":"Ian M. Davis","orcid":"0000-0002-6522-8036","position":6,"is_corresponding":false},{"id":792500,"name":"Siaresh Aziz","orcid":null,"position":7,"is_corresponding":false},{"id":475886,"name":"Georgia Dermentzaki","orcid":null,"position":8,"is_corresponding":false},{"id":343929,"name":"Francesco Lotti","orcid":"0000-0002-5104-9088","position":9,"is_corresponding":false},{"id":581378,"name":"Hynek Wichterle","orcid":"0000-0002-7817-0080","position":10,"is_corresponding":false},{"id":993371,"name":"Emily R. Lowry","orcid":"0000-0002-8412-3168","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:09:23.333150Z","pmid":"38617322","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":[]}