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Overexpression of Cystathionine gamma-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3
dc.creator | Snijder, Pauline M. | |
dc.creator | Baratashvili, Madina | |
dc.creator | Grzeschik, Nicola A. | |
dc.creator | Leuvenink, Henri G. D. | |
dc.creator | Kuijpers, Lucas | |
dc.creator | Huitema, Sippie | |
dc.creator | Schaap, Onno | |
dc.creator | Giepmans, Ben N. G. | |
dc.creator | Kuipers, Jeroen | |
dc.creator | Miljković, Jan Lj | |
dc.creator | Mitrović, Aleksandra D. | |
dc.creator | Bos, Eelke M. | |
dc.creator | Szabo, Csaba | |
dc.creator | Kampinga, Harm H. | |
dc.creator | Dijkers, Pascale F. | |
dc.creator | den Dunnen, Wilfred F. A. | |
dc.creator | Filipović, Miloš R. | |
dc.creator | van Goor, Harry | |
dc.creator | Sibon, Ody C. M. | |
dc.date.accessioned | 2018-11-22T00:33:41Z | |
dc.date.available | 2018-11-22T00:33:41Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 1076-1551 | |
dc.identifier.uri | https://cherry.chem.bg.ac.rs/handle/123456789/2255 | |
dc.description.abstract | Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine (polyQ) disorder caused by a CAG repeat expansion in the ataxin-3 (ATXN3) gene resulting in toxic protein aggregation. Inflammation and oxidative stress are considered secondary factors contributing to the progression of this neurodegenerative disease. There is no cure that halts or reverses the progressive neurodegeneration of SCA3. Here we show that overexpression of cystathionine.-lyase, a central enzyme in cysteine metabolism, is protective in a Drosophila model for SCA3. SCA3 flies show eye degeneration, increased oxidative stress, insoluble protein aggregates, reduced levels of protein persulfidation and increased activation of the innate immune response. Overexpression of Drosophila cystathionine.-lyase restores protein persulfidation, decreases oxidative stress, dampens the immune response and improves SCA3-associated tissue degeneration. Levels of insoluble protein aggregates are not altered; therefore, the data implicate a modifying role of cystathionine.-lyase in ameliorating the downstream consequence of protein aggregation leading to protection against SCA3-induced tissue degeneration. The cystathionine.-lyase expression is decreased in affected brain tissue of SCA3 patients, suggesting that enhancers of cystathionine.-lyase expression or activity are attractive candidates for future therapies. | en |
dc.publisher | Feinstein Inst Med Res, Manhasset | |
dc.relation | ZonMW [91111.006] | |
dc.relation | Jan Kornelis de Cock Foundation | |
dc.relation | VICI grant | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Molecular Medicine | |
dc.title | Overexpression of Cystathionine gamma-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3 | en |
dc.type | article | |
dc.rights.license | BY | |
dcterms.abstract | Сцхаап, Онно; Миљковиц, Јан Љ; Снијдер, Паулине М.; Баратасхвили, Мадина; Грзесцхик, Ницола A.; Леувенинк, Хенри Г. Д.; Куијперс, Луцас; Хуитема, Сиппие; Гиепманс, Бен Н. Г.; Куиперс, Јероен; Филиповиц, Милос Р.; Кампинга, Харм Х.; Митровић, Aлександра; Сибон, Одy Ц. М.; ван Гоор, Харрy; ден Дуннен, Wилфред Ф. A.; Дијкерс, Пасцале Ф.; Сзабо, Цсаба; Бос, Еелке М.; | |
dc.citation.volume | 21 | |
dc.citation.spage | 758 | |
dc.citation.epage | 768 | |
dc.identifier.wos | 000377271200009 | |
dc.identifier.doi | 10.2119/molmed.2015.00221 | |
dc.citation.other | 21: 758-768 | |
dc.citation.rank | M21 | |
dc.identifier.pmid | 26467707 | |
dc.description.other | Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3402] | |
dc.type.version | publishedVersion | |
dc.identifier.scopus | 2-s2.0-84975138044 | |
dc.identifier.fulltext | https://cherry.chem.bg.ac.rs/bitstream/id/9245/2253.pdf |