{"doi":"10.1101/2023.05.22.541784","title":"“Epidermal Eg5 promotes X-ROS dependent paclitaxel neurotoxicity”","abstract":"Abstract Taxanes are chemotherapeutic agents that induce microtubule modifications in cancer cells, resulting in cell cycle modifications and tumor remission. Here we show that paclitaxel, a widely used taxane, also induces microtubule modifications in healthy epidermal keratinocytes leading to chemotherapy-induced peripheral neuropathy (CIPN). Paclitaxel activates the cell cycle regulator, Kinesin-5 (Eg5), which promotes microtubule detyrosination and fasciculation (dfMT). Eg5 loss protects neurons from paclitaxel neurotoxicity, whereas keratinocyte-specific overexpression promotes axon degeneration. In vivo imaging and 3D reconstructions of dfMTs and nuclei, combined with mechanotransduction studies further show that dfMTs constrict keratinocyte nuclei, leading to nuclear Nox-dependent reactive oxygen species (X-ROS) formation upstream of MMP-13 and cutaneous sensory axon degeneration. This new insight facilitates our understanding of chemotherapy side effects and highlights the need for targeted therapies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":399433,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":348715,"name":"Anthony Cirrincione","orcid":"0000-0002-8133-9158","position":1,"is_corresponding":false},{"id":1175552,"name":"Natalie A. Schmidt","orcid":"0000-0001-7357-2841","position":2,"is_corresponding":false},{"id":1175889,"name":"Marie J Ugo","orcid":null,"position":3,"is_corresponding":false},{"id":1175890,"name":"Maria Celina Amaya Sanchez","orcid":null,"position":4,"is_corresponding":false},{"id":832757,"name":"Cassandra A. Reimonn","orcid":null,"position":5,"is_corresponding":false},{"id":21507,"name":"Stefan Wuchty","orcid":"0000-0001-8916-6522","position":6,"is_corresponding":false},{"id":349696,"name":"Adriana D. Pellegrini","orcid":null,"position":7,"is_corresponding":false},{"id":1175891,"name":"Leah RK Rude","orcid":null,"position":8,"is_corresponding":false},{"id":1175892,"name":"Leah G Pappalardo","orcid":null,"position":9,"is_corresponding":false},{"id":902094,"name":"Daniel P. Regan","orcid":"0000-0002-6363-0144","position":10,"is_corresponding":false},{"id":902097,"name":"Caitlin Howell","orcid":"0000-0002-9345-6642","position":11,"is_corresponding":false},{"id":1131534,"name":"Sybil Hrstka","orcid":"0000-0003-1442-5707","position":12,"is_corresponding":false},{"id":235319,"name":"Surendra Dasari","orcid":"0000-0002-7972-3556","position":13,"is_corresponding":false},{"id":420156,"name":"Thomas S. Lisse","orcid":"0000-0001-5557-3904","position":14,"is_corresponding":false},{"id":832326,"name":"Benjamin J. Harrison","orcid":"0000-0002-6078-5060","position":15,"is_corresponding":false},{"id":1175893,"name":"Mike Xiangxi Xu","orcid":null,"position":16,"is_corresponding":false},{"id":270410,"name":"Nathan P. Staff","orcid":"0000-0001-6760-3859","position":17,"is_corresponding":false},{"id":348719,"name":"Sandra Rieger","orcid":"0000-0002-9059-1670","position":18,"is_corresponding":false},{"id":1175551,"name":"Antonio Cádiz","orcid":"0000-0001-8955-5544","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T01:19:56.084411Z","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":[]}