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- W4387060885 abstract "Abstract TDP-43 proteinopathies including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by aggregation and mislocalization of the nucleic-acid binding protein TDP-43 and subsequent neuronal dysfunction. Here, we developed endogenous models of sporadic TDP-43 proteinopathy based on the principle that disease-associated TDP-43 acetylation at lysine 145 (K145) alters TDP-43 conformation, impairs RNA-binding capacity, and induces downstream mis-regulation of target genes. Expression of acetylation-mimic TDP-43 K145Q resulted in stress-induced nuclear TDP-43 foci and loss of TDP-43 function in primary mouse and human induced pluripotent stem cell (hiPSC)-derived cortical neurons. Mice harboring the TDP-43 K145Q mutation recapitulated key hallmarks of FTLD, including progressive TDP-43 phosphorylation and insolubility, TDP-43 mis-localization, transcriptomic and splicing alterations, and cognitive dysfunction. Our study supports a model in which TDP-43 acetylation drives neuronal dysfunction and cognitive decline through aberrant splicing and transcription of critical genes that regulate synaptic plasticity and stress response signaling. The neurodegenerative cascade initiated by TDP-43 acetylation recapitulates many aspects of human FTLD and provides a new paradigm to further interrogate TDP-43 proteinopathies." @default.
- W4387060885 created "2023-09-27" @default.
- W4387060885 creator A5001832821 @default.
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- W4387060885 date "2023-09-26" @default.
- W4387060885 modified "2023-10-12" @default.
- W4387060885 title "RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy" @default.
- W4387060885 cites W1525431743 @default.
- W4387060885 cites W1531617031 @default.
- W4387060885 cites W1560299838 @default.
- W4387060885 cites W1619082318 @default.
- W4387060885 cites W1833314573 @default.
- W4387060885 cites W1904847174 @default.
- W4387060885 cites W1965647277 @default.
- W4387060885 cites W1976564367 @default.
- W4387060885 cites W1982252060 @default.
- W4387060885 cites W1983316238 @default.
- W4387060885 cites W1984145170 @default.
- W4387060885 cites W1985955085 @default.
- W4387060885 cites W1987572257 @default.
- W4387060885 cites W1994580609 @default.
- W4387060885 cites W1995061803 @default.
- W4387060885 cites W1997809912 @default.
- W4387060885 cites W1998149691 @default.
- W4387060885 cites W1998512664 @default.
- W4387060885 cites W2002960835 @default.
- W4387060885 cites W2003618511 @default.
- W4387060885 cites W2006797111 @default.
- W4387060885 cites W2011396520 @default.
- W4387060885 cites W2019279972 @default.
- W4387060885 cites W2023691991 @default.
- W4387060885 cites W2024709136 @default.
- W4387060885 cites W2025500109 @default.
- W4387060885 cites W2027460468 @default.
- W4387060885 cites W2027594237 @default.
- W4387060885 cites W2036897871 @default.
- W4387060885 cites W2039385533 @default.
- W4387060885 cites W2040469179 @default.
- W4387060885 cites W2051876980 @default.
- W4387060885 cites W2052949958 @default.
- W4387060885 cites W2057181320 @default.
- W4387060885 cites W2057861812 @default.
- W4387060885 cites W2062858206 @default.
- W4387060885 cites W2065516118 @default.
- W4387060885 cites W2066901047 @default.
- W4387060885 cites W2073164785 @default.
- W4387060885 cites W2075588816 @default.
- W4387060885 cites W2080681771 @default.
- W4387060885 cites W2082314612 @default.
- W4387060885 cites W2082602037 @default.
- W4387060885 cites W2084394003 @default.
- W4387060885 cites W2084578579 @default.
- W4387060885 cites W2087786585 @default.
- W4387060885 cites W2093243836 @default.
- W4387060885 cites W2102026369 @default.
- W4387060885 cites W2106000656 @default.
- W4387060885 cites W2106158921 @default.
- W4387060885 cites W2107554012 @default.
- W4387060885 cites W2108244474 @default.
- W4387060885 cites W2108888119 @default.
- W4387060885 cites W2114120572 @default.
- W4387060885 cites W2116660354 @default.
- W4387060885 cites W2117597459 @default.
- W4387060885 cites W2125931517 @default.
- W4387060885 cites W2126812637 @default.
- W4387060885 cites W2126871157 @default.
- W4387060885 cites W2131174366 @default.
- W4387060885 cites W2134408741 @default.
- W4387060885 cites W2136057227 @default.
- W4387060885 cites W2136305293 @default.
- W4387060885 cites W2137048103 @default.
- W4387060885 cites W2141320958 @default.
- W4387060885 cites W2145817301 @default.
- W4387060885 cites W2146512944 @default.
- W4387060885 cites W2146946048 @default.
- W4387060885 cites W2151521848 @default.
- W4387060885 cites W2154417593 @default.
- W4387060885 cites W2155158396 @default.
- W4387060885 cites W2155633873 @default.
- W4387060885 cites W2157372514 @default.
- W4387060885 cites W2162625976 @default.
- W4387060885 cites W2167243829 @default.
- W4387060885 cites W2167279371 @default.
- W4387060885 cites W2167557855 @default.
- W4387060885 cites W2169456326 @default.