Search: onr:"swepub:oai:lup.lub.lu.se:1a4c1ad4-992e-484c-8b7d-adf5686ee455" > HTT-lowering revers...
Fältnamn | Indikatorer | Metadata |
---|---|---|
000 | 04210naa a2200577 4500 | |
001 | oai:lup.lub.lu.se:1a4c1ad4-992e-484c-8b7d-adf5686ee455 | |
003 | SwePub | |
008 | 160401s2014 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/43636352 URI |
024 | 7 | a https://doi.org/10.1093/brain/awt3552 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Traeger, Ulrike4 aut |
245 | 1 0 | a HTT-lowering reverses Huntington's disease immune dysfunction caused by NF kappa B pathway dysregulation |
264 | c 2014-01-22 | |
264 | 1 | b Oxford University Press (OUP),c 2014 |
520 | a Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NF kappa B pathway, whereby it interacts with IKK gamma, leads to increased degradation of I kappa B and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng |
653 | a Huntington's disease | |
653 | a immunology | |
653 | a myeloid cells | |
653 | a gene lowering | |
700 | 1 | a Andre, Ralph4 aut |
700 | 1 | a Lahiri, Nayana4 aut |
700 | 1 | a Magnusson-Lind, Annau Lund University,Lunds universitet,Biomarkörer vid hjärnsjukdomar,Forskargrupper vid Lunds universitet,Biomarkers in Brain Disease,Lund University Research Groups4 aut0 (Swepub:lu)med-a_m |
700 | 1 | a Weiss, Andreas4 aut |
700 | 1 | a Grueninger, Stephan4 aut |
700 | 1 | a McKinnon, Chris4 aut |
700 | 1 | a Sirinathsinghji, Eva4 aut |
700 | 1 | a Kahlon, Shira4 aut |
700 | 1 | a Pfister, Edith L.4 aut |
700 | 1 | a Moser, Roger4 aut |
700 | 1 | a Hummerich, Holger4 aut |
700 | 1 | a Antoniou, Michael4 aut |
700 | 1 | a Bates, Gillian P.4 aut |
700 | 1 | a Luthi-Carter, Ruth4 aut |
700 | 1 | a Lowdell, Mark W.4 aut |
700 | 1 | a Björkqvist, Mariau Lund University,Lunds universitet,Biomarkörer vid hjärnsjukdomar,Forskargrupper vid Lunds universitet,Biomarkers in Brain Disease,Lund University Research Groups4 aut0 (Swepub:lu)farm-mbj |
700 | 1 | a Ostroff, Gary R.4 aut |
700 | 1 | a Aronin, Neil4 aut |
700 | 1 | a Tabrizi, Sarah J.4 aut |
710 | 2 | a Biomarkörer vid hjärnsjukdomarb Forskargrupper vid Lunds universitet4 org |
773 | 0 | t Braind : Oxford University Press (OUP)g 137, s. 819-833q 137<819-833x 1460-2156x 0006-8950 |
856 | 4 | u http://dx.doi.org/10.1093/brain/awt355y FULLTEXT |
856 | 4 | u https://academic.oup.com/brain/article-pdf/137/3/819/13797635/awt355.pdf |
856 | 4 8 | u https://lup.lub.lu.se/record/4363635 |
856 | 4 8 | u https://doi.org/10.1093/brain/awt355 |
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
Copy and save the link in order to return to this view