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• W2143612940 abstract "Mutations in TARDBP, encoding TAR DNA-binding protein-43 (TDP-43), are associated with TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We compared wild-type TDP-43 and an ALS-associated mutant TDP-43 in vitro and in vivo. The A315T mutant enhances neurotoxicity and the formation of aberrant TDP-43 species, including protease-resistant fragments. The C terminus of TDP-43 shows sequence similarity to prion proteins. Synthetic peptides flanking residue 315 form amyloid fibrils in vitro and cause neuronal death in primary cultures. These data provide evidence for biochemical similarities between TDP-43 and prion proteins, raising the possibility that TDP-43 derivatives may cause spreading of the disease phenotype among neighboring neurons. Our work also suggests that decreasing the abundance of neurotoxic TDP-43 species, enhancing degradation or clearance of such TDP-43 derivatives and blocking the spread of the disease phenotype may have therapeutic potential for TDP-43 proteinopathies." @default.
• W2143612940 created "2016-06-24" @default.
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• W2143612940 date "2011-06-12" @default.
• W2143612940 modified "2023-09-28" @default.
• W2143612940 title "An ALS-associated mutation affecting TDP-43 enhances protein aggregation, fibril formation and neurotoxicity" @default.
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• W2143612940 doi "https://doi.org/10.1038/nsmb.2053" @default.
• W2143612940 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3357956" @default.
• W2143612940 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21666678" @default.
• W2143612940 hasPublicationYear "2011" @default.
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