{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yeh JY"],"funding":["National Health Research Institutes (NHRI)","NYMU | Brain Research Center, National Yang-Ming University (NYMU-BRC)","National Taiwan University","National Taiwan University ()","National Health Research Institutes","NYMU | Brain Research Center, National Yang-Ming University","National Science and Technology Council","National Science and Technology Council (NSTC)"],"pagination":["1091-1114"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11099080"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(5)"],"pubmed_abstract":["PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSC<sup>M70R</sup> variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSC<sup>M70R</sup> mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2."],"journal":["EMBO molecular medicine"],"pubmed_title":["A missense mutation in human INSC causes peripheral neuropathy."],"pmcid":["PMC11099080"],"funding_grant_id":["112-2628-B-007-004","112-2314-B-075 -034 -MY3","EX112-11228NI","The Featured Areas Research Center Program","112-2314-B-002 -016","112L895403","112-2636-B-007-008","111-2320-B-002-049-MY3","109-2314-B-075-044-MY3"],"pubmed_authors":["Hong CL","Hung YC","Lin S","Huang SY","Chao HC","Tzou FY","Chan CC","Yeh JY","Chou CT","Liao YC","Lee YC","Kennerson M","Hsiao CT","Lin YC","Li JL","Tsai YS","Chen WJ"],"additional_accession":[]},"is_claimable":false,"name":"A missense mutation in human INSC causes peripheral neuropathy.","description":"PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSC<sup>M70R</sup> variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSC<sup>M70R</sup> mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-01T17:29:25.392Z","creation":"2026-04-08T14:17:21.491Z"},"accession":"S-EPMC11099080","cross_references":{"pubmed":["38589651"],"doi":["10.1038/s44321-024-00062-w"]}}