{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Clark AJ"],"funding":["Brain Research UK","NINDS NIH HHS","Rosetrees","Wellcome Trust"],"pagination":["100345"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8324498"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["2(7)"],"pubmed_abstract":["Hereditary sensory neuropathy type 1 (HSN1) is caused by mutations in the <i>SPTLC1</i> or <i>SPTLC2</i> sub-units of the enzyme serine palmitoyltransferase, resulting in the production of toxic 1-deoxysphingolipid bases (DSBs). We used induced pluripotent stem cells (iPSCs) from patients with HSN1 to determine whether endogenous DSBs are neurotoxic, patho-mechanisms of toxicity and response to therapy. HSN1 iPSC-derived sensory neurons (iPSCdSNs) endogenously produce neurotoxic DSBs. Complex gangliosides, which are essential for membrane micro-domains and signaling, are reduced, and neurotrophin signaling is impaired, resulting in reduced neurite outgrowth. In HSN1 myelinating cocultures, we find a major disruption of nodal complex proteins after 8 weeks, which leads to complete myelin br"],"journal":["Cell reports. Medicine"],"pubmed_title":["An iPSC model of hereditary sensory neuropathy-1 reveals L-serine-responsive deficits in neuronal ganglioside composition and axoglial interactions."],"pmcid":["PMC8324498"],"funding_grant_id":["203141/Z/16/Z","U54 NS065712","M861","202747/Z/16/Z","202834/Z/16/Z","102645/Z/13/Z","201718-11"],"pubmed_authors":["Fugger N","Kalmar B","Kugathasan U","Bennett DL","Othman A","Greensmith L","Chu KH","Hornemann T","Clark AJ","Reilly MM","Baskozos G","Blesneac I","Laura M","Lone MA","Priestman DA","Platt FM","Wilson ER"],"additional_accession":[]},"is_claimable":false,"name":"An iPSC model of hereditary sensory neuropathy-1 reveals L-serine-responsive deficits in neuronal ganglioside composition and axoglial interactions.","description":"Hereditary sensory neuropathy type 1 (HSN1) is caused by mutations in the <i>SPTLC1</i> or <i>SPTLC2</i> sub-units of the enzyme serine palmitoyltransferase, resulting in the production of toxic 1-deoxysphingolipid bases (DSBs). We used induced pluripotent stem cells (iPSCs) from patients with HSN1 to determine whether endogenous DSBs are neurotoxic, patho-mechanisms of toxicity and response to therapy. HSN1 iPSC-derived sensory neurons (iPSCdSNs) endogenously produce neurotoxic DSBs. Complex gangliosides, which are essential for membrane micro-domains and signaling, are reduced, and neurotrophin signaling is impaired, resulting in reduced neurite outgrowth. In HSN1 myelinating cocultures, we find a major disruption of nodal complex proteins after 8 weeks, which leads to complete myelin br","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jul","modification":"2026-05-08T14:33:17.29Z","creation":"2022-02-11T02:18:10.873Z"},"accession":"S-EPMC8324498","cross_references":{"pubmed":["34337561"],"doi":["10.1016/j.xcrm.2021.100345"]}}