Matches in SemOpenAlex for { <https://semopenalex.org/work/W2951215750> ?p ?o ?g. }
- W2951215750 endingPage "104514" @default.
- W2951215750 startingPage "104514" @default.
- W2951215750 abstract "TAR-DNA binding protein 43 (TDP-43) is a multifunctional RNA binding protein directly implicated in the etiology of amyotrophic lateral sclerosis (ALS). Previous studies have demonstrated that loss of TDP-43 function leads to intracellular accumulation of non-coding repetitive element transcripts and double-stranded RNA (dsRNA). These events could cause immune activation and contribute to the neuroinflammation observed in ALS, but this possibility has not been investigated. Here, we knock down TDP-43 in primary rat astrocytes via siRNA, and we use RNA-seq, immunofluorescence, and immunoblotting to show that this results in: 1) accumulation of repetitive element transcripts and dsRNA; and 2) pro-inflammatory gene and protein expression consistent with innate immune signaling and astrocyte activation. We also show that both chemical inhibition and siRNA knockdown of protein kinase R (PKR), a dsRNA-activated kinase implicated in the innate immune response, block the expression of all activation markers assayed. Based on these findings, we suggest that intracellular accumulation of endogenous dsRNA may be a novel and important mechanism underlying the pathogenesis of ALS (and perhaps other neurodegenerative diseases), and that PKR inhibitors may have the potential to prevent reactive astrocytosis in ALS." @default.
- W2951215750 created "2019-06-27" @default.
- W2951215750 creator A5009588468 @default.
- W2951215750 creator A5025282582 @default.
- W2951215750 creator A5050614625 @default.
- W2951215750 creator A5075505395 @default.
- W2951215750 date "2019-12-01" @default.
- W2951215750 modified "2023-10-16" @default.
- W2951215750 title "TDP-43 knockdown causes innate immune activation via protein kinase R in astrocytes" @default.
- W2951215750 cites W1522823711 @default.
- W2951215750 cites W155253959 @default.
- W2951215750 cites W1934976150 @default.
- W2951215750 cites W1975110303 @default.
- W2951215750 cites W1976839582 @default.
- W2951215750 cites W1983335981 @default.
- W2951215750 cites W1984364760 @default.
- W2951215750 cites W1986611577 @default.
- W2951215750 cites W2003205286 @default.
- W2951215750 cites W2003618511 @default.
- W2951215750 cites W2004820588 @default.
- W2951215750 cites W2007664874 @default.
- W2951215750 cites W2008334829 @default.
- W2951215750 cites W2013806485 @default.
- W2951215750 cites W2016737975 @default.
- W2951215750 cites W2017217665 @default.
- W2951215750 cites W2024882157 @default.
- W2951215750 cites W2025312384 @default.
- W2951215750 cites W2025862653 @default.
- W2951215750 cites W2027720028 @default.
- W2951215750 cites W2034632760 @default.
- W2951215750 cites W2038963685 @default.
- W2951215750 cites W2042930414 @default.
- W2951215750 cites W2044345058 @default.
- W2951215750 cites W2047265916 @default.
- W2951215750 cites W2051541780 @default.
- W2951215750 cites W2053362200 @default.
- W2951215750 cites W2054811674 @default.
- W2951215750 cites W2065533930 @default.
- W2951215750 cites W2065557328 @default.
- W2951215750 cites W2071670416 @default.
- W2951215750 cites W2073073462 @default.
- W2951215750 cites W2074602312 @default.
- W2951215750 cites W2074692187 @default.
- W2951215750 cites W2086588049 @default.
- W2951215750 cites W2086676762 @default.
- W2951215750 cites W2089188450 @default.
- W2951215750 cites W2094315474 @default.
- W2951215750 cites W2099671775 @default.
- W2951215750 cites W2109192152 @default.
- W2951215750 cites W2111586778 @default.
- W2951215750 cites W2116710635 @default.
- W2951215750 cites W2119267300 @default.
- W2951215750 cites W2126986156 @default.
- W2951215750 cites W2131198526 @default.
- W2951215750 cites W2136949432 @default.
- W2951215750 cites W2141760092 @default.
- W2951215750 cites W2144507462 @default.
- W2951215750 cites W2146546145 @default.
- W2951215750 cites W2150368381 @default.
- W2951215750 cites W2153328565 @default.
- W2951215750 cites W2154520196 @default.
- W2951215750 cites W2164104132 @default.
- W2951215750 cites W2169076520 @default.
- W2951215750 cites W2170485551 @default.
- W2951215750 cites W2289154867 @default.
- W2951215750 cites W2291649422 @default.
- W2951215750 cites W2337710586 @default.
- W2951215750 cites W2478122494 @default.
- W2951215750 cites W2572710398 @default.
- W2951215750 cites W2607829140 @default.
- W2951215750 cites W2626250818 @default.
- W2951215750 cites W2700330585 @default.
- W2951215750 cites W2735217968 @default.
- W2951215750 cites W2735951425 @default.
- W2951215750 cites W2737812443 @default.
- W2951215750 cites W2761494190 @default.
- W2951215750 cites W2769119592 @default.
- W2951215750 cites W2790179543 @default.
- W2951215750 cites W2797930701 @default.
- W2951215750 cites W2920893206 @default.
- W2951215750 cites W2952199982 @default.
- W2951215750 cites W4321317599 @default.
- W2951215750 doi "https://doi.org/10.1016/j.nbd.2019.104514" @default.
- W2951215750 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6834892" @default.
- W2951215750 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31229690" @default.
- W2951215750 hasPublicationYear "2019" @default.
- W2951215750 type Work @default.
- W2951215750 sameAs 2951215750 @default.
- W2951215750 citedByCount "36" @default.
- W2951215750 countsByYear W29512157502019 @default.
- W2951215750 countsByYear W29512157502020 @default.
- W2951215750 countsByYear W29512157502021 @default.
- W2951215750 countsByYear W29512157502022 @default.
- W2951215750 countsByYear W29512157502023 @default.
- W2951215750 crossrefType "journal-article" @default.
- W2951215750 hasAuthorship W2951215750A5009588468 @default.
- W2951215750 hasAuthorship W2951215750A5025282582 @default.
- W2951215750 hasAuthorship W2951215750A5050614625 @default.