{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Erwin AL"],"funding":["NIA NIH HHS","NINDS NIH HHS","NIGMS NIH HHS","NIH HHS"],"pubmed_abstract":["Nuclear exclusion and cytoplasmic accumulation of the RNA-binding protein TDP43 are characteristic of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite this, the origin and ultrastructure of cytosolic TDP43 deposits remain unknown. Accumulating evidence suggests that abnormal RNA homeostasis can drive pathological TDP43 mislocalization, enhancing RNA misprocessing due to loss of nuclear TDP43 and engendering a cycle that ends in cell death. Here, we show that adding small monovalent oligonucleotides successfully recapitulates pathological TDP43 mislocalization and aggregation in iPSC-derived neurons (iNeurons). By employing a multimodal <i>in situ</i> cryo-correlative light and electron microscopy pipeline, we examine how RNA influences the localizat"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.08.19.608477"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11370468"],"repository":["biostudies-literature"],"pubmed_title":["Molecular Visualization of Neuronal TDP43 Pathology <i>In Situ</i>."],"pmcid":["PMC11370468"],"funding_grant_id":["P30 AG072931","S10 OD030275","DP2 GM150019","F31 NS134123","T32 GM007544","R01 NS113943","R01 NS097542","T32 GM141840","R35 GM128592","R56 NS128110"],"pubmed_authors":["Baldridge RD","Attili D","Thomas D","Bekier M","Mosalaganti S","Tank EMH","Barmada SJ","Chang ML","Li X","Pinarbasi ES","Brant TS","Russ JE","Hahn T","Dykstra M","Sutanto R","Fernandez MG","Erwin AL"],"additional_accession":[]},"is_claimable":false,"name":"Molecular Visualization of Neuronal TDP43 Pathology <i>In Situ</i>.","description":"Nuclear exclusion and cytoplasmic accumulation of the RNA-binding protein TDP43 are characteristic of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite this, the origin and ultrastructure of cytosolic TDP43 deposits remain unknown. Accumulating evidence suggests that abnormal RNA homeostasis can drive pathological TDP43 mislocalization, enhancing RNA misprocessing due to loss of nuclear TDP43 and engendering a cycle that ends in cell death. Here, we show that adding small monovalent oligonucleotides successfully recapitulates pathological TDP43 mislocalization and aggregation in iPSC-derived neurons (iNeurons). By employing a multimodal <i>in situ</i> cryo-correlative light and electron microscopy pipeline, we examine how RNA influences the localizat","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2026-04-21T03:21:28.757Z","creation":"2025-04-21T21:48:48.892Z"},"accession":"S-EPMC11370468","cross_references":{"pubmed":["39229019"],"doi":["10.1101/2024.08.19.608477"]}}