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dc.contributor.authorMalik, Anna R
dc.contributor.authorLiszewska, Ewa
dc.contributor.authorSkalecka, Agnieszka
dc.contributor.authorUrbanska, Malgorzata
dc.contributor.authorIyer, Anand M
dc.contributor.authorSwiech, Lukasz J
dc.contributor.authorPerycz, Malgorzata
dc.contributor.authorParobczak, Kamil
dc.contributor.authorPietruszka, Patrycja
dc.contributor.authorZarebska, Malgorzata M
dc.contributor.authorMacias, Matylda
dc.contributor.authorKotulska, Katarzyna
dc.contributor.authorBorkowska, Julita
dc.contributor.authorGrajkowska, Wieslawa
dc.contributor.authorTyburczy, Magdalena E
dc.contributor.authorJozwiak, Sergiusz
dc.contributor.authorKwiatkowski, David J
dc.contributor.authorAronica, Eleonora
dc.contributor.authorJaworski, Jacek
dc.date.accessioned2015-09-01T18:08:57Z
dc.date.available2015-09-01T18:08:57Z
dc.date.issued2015-07-30
dc.identifier.citationActa Neuropathologica Communications. 2015 Jul 30;3(1):48
dc.identifier.urihttp://dx.doi.org/10.1186/s40478-015-0225-z
dc.identifier.urihttp://hdl.handle.net/10724/31953
dc.description.abstractAbstract Introduction Tuberous sclerosis complex (TSC) is a genetic disease resulting from mutation in TSC1 or TSC2 and subsequent hyperactivation of mammalian Target of Rapamycin (mTOR). Common TSC features include brain lesions, such as cortical tubers and subependymal giant cell astrocytomas (SEGAs). However, the current treatment with mTOR inhibitors has critical limitations. We aimed to identify new targets for TSC pharmacotherapy. Results The results of our shRNA screen point to glutamate-cysteine ligase catalytic subunit (GCLC), a key enzyme in glutathione synthesis, as a contributor to TSC-related phenotype. GCLC inhibition increased cellular stress and reduced mTOR hyperactivity in TSC2-depleted neurons and SEGA-derived cells. Moreover, patients’ brain tubers showed elevated GCLC and stress markers expression. Finally, GCLC inhibition led to growth arrest and death of SEGA-derived cells. Conclusions We describe GCLC as a part of redox adaptation in TSC, needed for overgrowth and survival of mutant cells, and provide a potential novel target for SEGA treatment.
dc.titleTuberous sclerosis complex neuropathology requires glutamate-cysteine ligase
dc.typeJournal Article
dc.date.updated2015-07-29T19:05:41Z
dc.language.rfc3066en
dc.rights.holderMalik et al.


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