{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Xiao Q"],"pubmed_abstract":["Tau accumulation is a central driver of neurodegenerative diseases, yet strategies to promote its clearance remain limited. We developed a HaloTag-4R-Tau sensor in human iPSC-derived neurons (iNeurons) that enables sensitive monitoring the kinetics of both lysosomal partitioning and overall cellular turnover of tau. Using this sensor, we screened a small collection of small-molecule modulators of proteostasis network function and identified Neddylation inhibition by Pevonedistat as a robust promoter of soluble tau degradation. Mechanistic analysis including proteomic profiling revealed that Neddylation inhibition hastens HaloTag-Tau clearance via compensatory activation of a proteasome-dependent pathway(s) as well as the autophagy-lysosome pathway. Our findings establish a powerful tool fo"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2026.01.28.702105"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12874043"],"repository":["biostudies-literature"],"pubmed_title":["A HaloTag-4R-Tau Pulse-Chase Sensor Reveals Neddylation Inhibition Promotes Degradation of Tau in iNeurons."],"pmcid":["PMC12874043"],"pubmed_authors":["Gao Z","Allen S","Garza D","Morimoto RI","Kelly JW","Xiao Q"],"additional_accession":[]},"is_claimable":false,"name":"A HaloTag-4R-Tau Pulse-Chase Sensor Reveals Neddylation Inhibition Promotes Degradation of Tau in iNeurons.","description":"Tau accumulation is a central driver of neurodegenerative diseases, yet strategies to promote its clearance remain limited. We developed a HaloTag-4R-Tau sensor in human iPSC-derived neurons (iNeurons) that enables sensitive monitoring the kinetics of both lysosomal partitioning and overall cellular turnover of tau. Using this sensor, we screened a small collection of small-molecule modulators of proteostasis network function and identified Neddylation inhibition by Pevonedistat as a robust promoter of soluble tau degradation. Mechanistic analysis including proteomic profiling revealed that Neddylation inhibition hastens HaloTag-Tau clearance via compensatory activation of a proteasome-dependent pathway(s) as well as the autophagy-lysosome pathway. Our findings establish a powerful tool fo","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-07-09T11:27:11.061Z","creation":"2026-07-09T10:47:17.294Z"},"accession":"S-EPMC12874043","cross_references":{"pubmed":["41659571"],"doi":["10.64898/2026.01.28.702105"]}}