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- W3136665645 abstract "Abstract TDP-43 inclusions enriched in C-terminal fragments of ~25kDa (“TDP-25”) are associated with neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we analyzed gain-of-function mechanisms of TDP-25 combining cryo-electron tomography, proteomics and functional assays. TDP-25 inclusions are amorphous with gel-like biophysical properties and sequester proteasomes adopting exclusively substrate-processing conformations. This leads to proteostasis impairment, further enhanced by pathogenic mutations. These findings bolster the importance of proteasome dysfunction in ALS/FTD." @default.
- W3136665645 created "2021-03-29" @default.
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- W3136665645 date "2021-03-16" @default.
- W3136665645 modified "2023-09-25" @default.
- W3136665645 title "Gel-like inclusions of C-terminal fragments of TDP-43 sequester and inhibit proteasomes in neurons" @default.
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- W3136665645 doi "https://doi.org/10.1101/2021.03.15.435268" @default.
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