{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["300(5)"],"submitter":["Pokrishevsky E"],"funding":["ALS Society of Canada","R Howard Webster Foundation","ProMIS Neurosciences Inc"],"pubmed_abstract":["Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons. Neuronal superoxide dismutase-1 (SOD1) inclusion bodies are characteristic of familial ALS with SOD1 mutations, while a hallmark of sporadic ALS is inclusions containing aggregated WT TAR DNA-binding protein 43 (TDP-43). We show here that co-expression of mutant or WT TDP-43 with SOD1 leads to misfolding of endogenous SOD1 and aggregation of SOD1 reporter protein SOD1<sup>G85R</sup>-GFP in human cell cultures and promotes synergistic axonopathy in zebrafish. Intriguingly, this pathological interaction is modulated by natively solvent-exposed tryptophans in SOD1 (tryptophan-32) and TDP-43 RNA-recognition motif RRM1 (tryptophan-172), in concert with natively sequestered TDP-43 N-terminal domain tryptop"],"journal":["The Journal of biological chemistry"],"pagination":["107207"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11087967"],"repository":["biostudies-literature"],"pubmed_title":["Tryptophan residues in TDP-43 and SOD1 modulate the cross-seeding and toxicity of SOD1."],"pmcid":["PMC11087967"],"pubmed_authors":["Pozzi S","Cashman NR","Julien JP","McAlary L","Dijkstra A","DuVal MG","Roman A","Plotkin SS","Pokrishevsky E","Louadi S","Allison WT"],"additional_accession":[]},"is_claimable":false,"name":"Tryptophan residues in TDP-43 and SOD1 modulate the cross-seeding and toxicity of SOD1.","description":"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons. Neuronal superoxide dismutase-1 (SOD1) inclusion bodies are characteristic of familial ALS with SOD1 mutations, while a hallmark of sporadic ALS is inclusions containing aggregated WT TAR DNA-binding protein 43 (TDP-43). We show here that co-expression of mutant or WT TDP-43 with SOD1 leads to misfolding of endogenous SOD1 and aggregation of SOD1 reporter protein SOD1<sup>G85R</sup>-GFP in human cell cultures and promotes synergistic axonopathy in zebrafish. Intriguingly, this pathological interaction is modulated by natively solvent-exposed tryptophans in SOD1 (tryptophan-32) and TDP-43 RNA-recognition motif RRM1 (tryptophan-172), in concert with natively sequestered TDP-43 N-terminal domain tryptop","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-02T09:01:30.852Z","creation":"2026-04-16T03:13:12.719Z"},"accession":"S-EPMC11087967","cross_references":{"pubmed":["38522514"],"doi":["10.1016/j.jbc.2024.107207"]}}