Small interfering RNA-mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema

Nicolai E Savaskan; Alexandra Heckel; Eric Hahnen; Tobias Engelhorn; Arnd Doerfler; Oliver Ganslandt; Christopher Nimsky; Michael Buchfelder; Ilker Y Eyüpoglu

doi:10.1038/nm1772

Small interfering RNA-mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema

Nat Med. 2008 Jun;14(6):629-32. doi: 10.1038/nm1772. Epub 2008 May 11.

Authors

Nicolai E Savaskan¹, Alexandra Heckel, Eric Hahnen, Tobias Engelhorn, Arnd Doerfler, Oliver Ganslandt, Christopher Nimsky, Michael Buchfelder, Ilker Y Eyüpoglu

Affiliation

¹ Brain Research Institute, Swiss Federal Institute of Technology & University Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.

PMID: 18469825
DOI: 10.1038/nm1772

Abstract

Neurodegeneration and brain edema are hallmarks of human malignant brain tumors. Here we show that genetic or pharmacological inhibition of the glutamate transporter xCT (X(c-) system, encoded by SLC7a11) in vivo leads to abrogated neurodegeneration, attenuated perifocal edema and prolonged survival. These results show a crucial role for xCT in glioma-induced neurodegeneration and brain edema, corroborating the concept that edema formation may be in part a consequence of peritumoral cell death.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Transport System y+ / antagonists & inhibitors
Amino Acid Transport System y+ / genetics*
Amino Acid Transport System y+ / metabolism
Brain Edema / pathology*
Case-Control Studies
Cell Line, Tumor
Gene Silencing*
Glioma / genetics*
Glioma / pathology
Humans
Neurodegenerative Diseases / pathology*
RNA Interference
RNA, Small Interfering / metabolism*

Substances

Amino Acid Transport System y+
RNA, Small Interfering
SLC7A11 protein, human