FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2144720497> ?p ?o ?g. }

• W2144720497 endingPage "3515" @default.
• W2144720497 startingPage "3502" @default.
• W2144720497 abstract "Early-onset torsion dystonia is the most severe heritable form of dystonia, a human movement disorder that typically starts during a developmental window in early adolescence. Deletion in the DYT1 gene, encoding the torsinA protein, is responsible for this dominantly inherited disorder, which is non-degenerative and exhibits reduced penetrance among carriers. Here, we explore the hypothesis that deficits in torsinA function result in an increased vulnerability to stress associated with protein folding and processing in the endoplasmic reticulum (ER), where torsinA is located. Using an in vivo quantitative readout for the ER stress response, we evaluated the consequences of torsinA mutations in transgenic nematodes expressing variants of human torsinA. This analysis revealed that, normally, torsinA serves a protective function to maintain a homeostatic threshold against ER stress. Furthermore, we show that the buffering capacity of torsinA is greatly diminished by the DYT1 -associated deletion or mutations that prevent its translocation to the ER, block ATPase activity, or increase the levels of torsinA in the nuclear envelope versus ER. Combinations of transgenic Caenorhabditis elegans designed to mimic clinically relevant genetic modifiers of disease susceptibility also exhibit a direct functional correlation to changes in the ER stress response. Furthermore, using mouse embryonic fibroblasts (MEFs) from torsinA knockout mice, we demonstrated that loss of endogenous torsinA results in enhanced sensitivity to ER stress. This study extends our understanding of molecular mechanisms underlying dystonia, and establishes a new functional paradigm to evaluate therapeutic strategies to compensate for reduced torsinA activity in the ER as a means to restore homeostatic balance and neuronal function." @default.
• W2144720497 created "2016-06-24" @default.
• W2144720497 creator A5001281517 @default.
• W2144720497 creator A5015274628 @default.
• W2144720497 creator A5025987228 @default.
• W2144720497 creator A5033267154 @default.
• W2144720497 creator A5043519060 @default.
• W2144720497 creator A5059573074 @default.
• W2144720497 creator A5061741726 @default.
• W2144720497 creator A5066168948 @default.
• W2144720497 creator A5075243595 @default.
• W2144720497 creator A5091597765 @default.
• W2144720497 date "2010-06-28" @default.
• W2144720497 modified "2023-10-06" @default.
• W2144720497 title "The early-onset torsion dystonia-associated protein, torsinA, is a homeostatic regulator of endoplasmic reticulum stress response" @default.
• W2144720497 cites W1490093678 @default.
• W2144720497 cites W1505317673 @default.
• W2144720497 cites W1507128123 @default.
• W2144720497 cites W1944127002 @default.
• W2144720497 cites W1965843055 @default.
• W2144720497 cites W1971497139 @default.
• W2144720497 cites W1979193480 @default.
• W2144720497 cites W1980641489 @default.
• W2144720497 cites W1986720797 @default.
• W2144720497 cites W1986737010 @default.
• W2144720497 cites W1988259487 @default.
• W2144720497 cites W1995185770 @default.
• W2144720497 cites W1997720284 @default.
• W2144720497 cites W2015748354 @default.
• W2144720497 cites W2020102061 @default.
• W2144720497 cites W2025693497 @default.
• W2144720497 cites W2035198471 @default.
• W2144720497 cites W2036052128 @default.
• W2144720497 cites W2039027561 @default.
• W2144720497 cites W2040010470 @default.
• W2144720497 cites W2053202443 @default.
• W2144720497 cites W2053470799 @default.
• W2144720497 cites W2055956984 @default.
• W2144720497 cites W2057281288 @default.
• W2144720497 cites W2057913897 @default.
• W2144720497 cites W2058363047 @default.
• W2144720497 cites W2058469726 @default.
• W2144720497 cites W2059265460 @default.
• W2144720497 cites W2067455339 @default.
• W2144720497 cites W2070579053 @default.
• W2144720497 cites W2072306758 @default.
• W2144720497 cites W2074802067 @default.
• W2144720497 cites W2076159058 @default.
• W2144720497 cites W2083605841 @default.
• W2144720497 cites W2084752631 @default.
• W2144720497 cites W2088078969 @default.
• W2144720497 cites W2091151964 @default.
• W2144720497 cites W2095518178 @default.
• W2144720497 cites W2098691225 @default.
• W2144720497 cites W2107801170 @default.
• W2144720497 cites W2112126058 @default.
• W2144720497 cites W2118076431 @default.
• W2144720497 cites W2118742277 @default.
• W2144720497 cites W2122163057 @default.
• W2144720497 cites W2125943338 @default.
• W2144720497 cites W2130203692 @default.
• W2144720497 cites W2130566610 @default.
• W2144720497 cites W2132296982 @default.
• W2144720497 cites W2133119603 @default.
• W2144720497 cites W2136356801 @default.
• W2144720497 cites W2137275982 @default.
• W2144720497 cites W2137755719 @default.
• W2144720497 cites W2150261685 @default.
• W2144720497 cites W2152542101 @default.
• W2144720497 cites W2154455082 @default.
• W2144720497 cites W2156407587 @default.
• W2144720497 cites W2156990953 @default.
• W2144720497 cites W2160289007 @default.
• W2144720497 cites W2162679859 @default.
• W2144720497 doi "https://doi.org/10.1093/hmg/ddq266" @default.
• W2144720497 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3606045" @default.
• W2144720497 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20584926" @default.
• W2144720497 hasPublicationYear "2010" @default.
• W2144720497 type Work @default.
• W2144720497 sameAs 2144720497 @default.
• W2144720497 citedByCount "91" @default.
• W2144720497 countsByYear W21447204972012 @default.
• W2144720497 countsByYear W21447204972013 @default.
• W2144720497 countsByYear W21447204972014 @default.
• W2144720497 countsByYear W21447204972015 @default.
• W2144720497 countsByYear W21447204972016 @default.
• W2144720497 countsByYear W21447204972017 @default.
• W2144720497 countsByYear W21447204972018 @default.
• W2144720497 countsByYear W21447204972019 @default.
• W2144720497 countsByYear W21447204972020 @default.
• W2144720497 countsByYear W21447204972021 @default.
• W2144720497 countsByYear W21447204972022 @default.
• W2144720497 countsByYear W21447204972023 @default.
• W2144720497 crossrefType "journal-article" @default.
• W2144720497 hasAuthorship W2144720497A5001281517 @default.
• W2144720497 hasAuthorship W2144720497A5015274628 @default.
• W2144720497 hasAuthorship W2144720497A5025987228 @default.
• W2144720497 hasAuthorship W2144720497A5033267154 @default.

• next