FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200605055> ?p ?o ?g. }

• W4200605055 abstract "ABSTRACT Previous studies have revealed that dysregulation of long interspersed nuclear element 1 (LINE-1), a dominant class of transposable elements in the human genome, correlates with neurodegeneration 1–3 . Yet whether LINE-1 dysregulation is causal to disease pathogenesis has not been proven directly. Here, we demonstrate that expression of evolutionarily younger LINE-1 families is elevated in the cerebella of ataxia telangiectasia (AT) patients, which was correlated with extensive downregulation of epigenetic silencers. To examine whether LINE-1 activation causes neurologic disease, we established an approach to directly target and activate the promoter of a young family of LINE-1 in mice. LINE-1 activation in the cerebellum was sufficient to lead to robust progressive ataxia. Purkinje cells in the diseased mice exhibited marked electrophysiological dysfunctions and degeneration with a significant accumulation of cytoplasmic ribonucleoprotein LINE-1Orf1p aggregates, endoplasmic reticulum (ER) stress, and DNA damage. Treatment with lamivudine, a nucleoside reverse transcriptase inhibitor, blunted the disease progression by reducing DNA damage, attenuating gliosis and interferon gene signature, and recovering the loss of key functional molecules for calcium homeostasis in Purkinje cells. This study provides direct evidence that young LINE-1 activation drives ataxia phenotype, and points to its pleiotropic effects leading to DNA damage, inflammation, and dysfunction and degeneration of neurons." @default.
• W4200605055 created "2021-12-31" @default.
• W4200605055 creator A5003734252 @default.
• W4200605055 creator A5010263068 @default.
• W4200605055 creator A5011056392 @default.
• W4200605055 creator A5019724131 @default.
• W4200605055 creator A5023884031 @default.
• W4200605055 creator A5036389887 @default.
• W4200605055 creator A5042714892 @default.
• W4200605055 creator A5046136462 @default.
• W4200605055 creator A5047535476 @default.
• W4200605055 creator A5051738749 @default.
• W4200605055 creator A5053424653 @default.
• W4200605055 creator A5065468368 @default.
• W4200605055 creator A5068028435 @default.
• W4200605055 creator A5071844727 @default.
• W4200605055 creator A5072197843 @default.
• W4200605055 creator A5072411299 @default.
• W4200605055 creator A5080631441 @default.
• W4200605055 creator A5083196693 @default.
• W4200605055 date "2021-12-03" @default.
• W4200605055 modified "2023-10-17" @default.
• W4200605055 title "LINE-1 activation in the cerebellum drives ataxia" @default.
• W4200605055 cites W1966682237 @default.
• W4200605055 cites W1974888639 @default.
• W4200605055 cites W1977823971 @default.
• W4200605055 cites W1987332588 @default.
• W4200605055 cites W2001806616 @default.
• W4200605055 cites W2042086471 @default.
• W4200605055 cites W2047347093 @default.
• W4200605055 cites W2049867157 @default.
• W4200605055 cites W2062238129 @default.
• W4200605055 cites W2064815984 @default.
• W4200605055 cites W2079414750 @default.
• W4200605055 cites W2082855639 @default.
• W4200605055 cites W2085474187 @default.
• W4200605055 cites W2089198803 @default.
• W4200605055 cites W2102619694 @default.
• W4200605055 cites W2111203527 @default.
• W4200605055 cites W2124210271 @default.
• W4200605055 cites W2127476876 @default.
• W4200605055 cites W2127862779 @default.
• W4200605055 cites W2142867361 @default.
• W4200605055 cites W2145214649 @default.
• W4200605055 cites W2158217645 @default.
• W4200605055 cites W2169456326 @default.
• W4200605055 cites W2179438025 @default.
• W4200605055 cites W2585230893 @default.
• W4200605055 cites W2588443411 @default.
• W4200605055 cites W2601885162 @default.
• W4200605055 cites W2737372261 @default.
• W4200605055 cites W2745112353 @default.
• W4200605055 cites W2782844203 @default.
• W4200605055 cites W2783322400 @default.
• W4200605055 cites W2801545642 @default.
• W4200605055 cites W2811106513 @default.
• W4200605055 cites W2884857090 @default.
• W4200605055 cites W2884899270 @default.
• W4200605055 cites W2901283619 @default.
• W4200605055 cites W2905289636 @default.
• W4200605055 cites W2911642321 @default.
• W4200605055 cites W2921681769 @default.
• W4200605055 cites W2942885970 @default.
• W4200605055 cites W2951551910 @default.
• W4200605055 cites W2960183779 @default.
• W4200605055 cites W2966850360 @default.
• W4200605055 cites W2997384931 @default.
• W4200605055 cites W3030834164 @default.
• W4200605055 cites W3031048909 @default.
• W4200605055 cites W3160290721 @default.
• W4200605055 cites W3188425922 @default.
• W4200605055 cites W3193349476 @default.
• W4200605055 doi "https://doi.org/10.1101/2021.12.03.471151" @default.
• W4200605055 hasPublicationYear "2021" @default.
• W4200605055 type Work @default.
• W4200605055 citedByCount "0" @default.
• W4200605055 crossrefType "posted-content" @default.
• W4200605055 hasAuthorship W4200605055A5003734252 @default.
• W4200605055 hasAuthorship W4200605055A5010263068 @default.
• W4200605055 hasAuthorship W4200605055A5011056392 @default.
• W4200605055 hasAuthorship W4200605055A5019724131 @default.
• W4200605055 hasAuthorship W4200605055A5023884031 @default.
• W4200605055 hasAuthorship W4200605055A5036389887 @default.
• W4200605055 hasAuthorship W4200605055A5042714892 @default.
• W4200605055 hasAuthorship W4200605055A5046136462 @default.
• W4200605055 hasAuthorship W4200605055A5047535476 @default.
• W4200605055 hasAuthorship W4200605055A5051738749 @default.
• W4200605055 hasAuthorship W4200605055A5053424653 @default.
• W4200605055 hasAuthorship W4200605055A5065468368 @default.
• W4200605055 hasAuthorship W4200605055A5068028435 @default.
• W4200605055 hasAuthorship W4200605055A5071844727 @default.
• W4200605055 hasAuthorship W4200605055A5072197843 @default.
• W4200605055 hasAuthorship W4200605055A5072411299 @default.
• W4200605055 hasAuthorship W4200605055A5080631441 @default.
• W4200605055 hasAuthorship W4200605055A5083196693 @default.
• W4200605055 hasBestOaLocation W42006050552 @default.
• W4200605055 hasConcept C104317684 @default.
• W4200605055 hasConcept C126322002 @default.
• W4200605055 hasConcept C127561419 @default.
• W4200605055 hasConcept C143425029 @default.

• next