{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chongtham A"],"funding":["CHDI Foundation Los Angeles","NINDS NIH HHS","NIH"],"pagination":["105517"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8943833"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["159"],"pubmed_abstract":["Huntington's disease (HD) is a genetically inherited neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) repeat in the exon-1 of huntingtin protein (HTT). The expanded polyQ enhances the amyloidogenic propensity of HTT exon 1 (HTTex1), which forms a heterogeneous mixture of assemblies with a broad neurotoxicity spectrum. While predominantly intracellular, monomeric and aggregated mutant HTT species are also present in the cerebrospinal fluids of HD patients, however, their biological properties are not well understood. To explore the role of extracellular mutant HTT in aggregation and toxicity, we investigated the uptake and amplification of recombinant HTTex1 assemblies in cell culture models. We find that small HTTex1 fibrils preferentially enter human neurons and t"],"journal":["Neurobiology of disease"],"pubmed_title":["Amplification of neurotoxic HTTex1 assemblies in human neurons."],"pmcid":["PMC8943833"],"funding_grant_id":["R01 NS084345","R01 NS118859","A-12890","A-12640"],"pubmed_authors":["Kennedy MB","Khoshnan A","Rawat A","Isas JM","Mastro T","Yoo JH","Langen R","Chongtham A","Pandey NK"],"additional_accession":[]},"is_claimable":false,"name":"Amplification of neurotoxic HTTex1 assemblies in human neurons.","description":"Huntington's disease (HD) is a genetically inherited neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) repeat in the exon-1 of huntingtin protein (HTT). The expanded polyQ enhances the amyloidogenic propensity of HTT exon 1 (HTTex1), which forms a heterogeneous mixture of assemblies with a broad neurotoxicity spectrum. While predominantly intracellular, monomeric and aggregated mutant HTT species are also present in the cerebrospinal fluids of HD patients, however, their biological properties are not well understood. To explore the role of extracellular mutant HTT in aggregation and toxicity, we investigated the uptake and amplification of recombinant HTTex1 assemblies in cell culture models. We find that small HTTex1 fibrils preferentially enter human neurons and t","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2025-04-04T07:43:18.523Z","creation":"2025-04-04T07:43:18.523Z"},"accession":"S-EPMC8943833","cross_references":{"pubmed":["34563643"],"doi":["10.1016/j.nbd.2021.105517"]}}