Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits.
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Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. / Tang, Sung-Chun; Arumugam, Thiruma V; Xu, Xiangru; Cheng, Aiwu; Mughal, Mohamed R; Jo, Dong Gyu; Lathia, Justin D; Siler, Dominic A; Chigurupati, Srinivasulu; Ouyang, Xin; Magnus, Tim; Camandola, Simonetta; Mattson, Mark P.
in: P NATL ACAD SCI USA, Jahrgang 104, Nr. 34, 34, 2007, S. 13798-13803.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits.
AU - Tang, Sung-Chun
AU - Arumugam, Thiruma V
AU - Xu, Xiangru
AU - Cheng, Aiwu
AU - Mughal, Mohamed R
AU - Jo, Dong Gyu
AU - Lathia, Justin D
AU - Siler, Dominic A
AU - Chigurupati, Srinivasulu
AU - Ouyang, Xin
AU - Magnus, Tim
AU - Camandola, Simonetta
AU - Mattson, Mark P
PY - 2007
Y1 - 2007
N2 - The innate immune system senses the invasion of pathogenic microorganisms and tissue injury through Toll-like receptors (TLR), a mechanism thought to be limited to immune cells. We now report that neurons express several TLRs, and that the levels of TLR2 and -4 are increased in neurons in response to IFN-gamma stimulation and energy deprivation. Neurons from both TLR2 knockout and -4 mutant mice were protected against energy deprivation-induced cell death, which was associated with decreased activation of a proapoptotic signaling cascade involving jun N-terminal kinase and the transcription factor AP-1. TLR2 and -4 expression was increased in cerebral cortical neurons in response to ischemia/reperfusion injury, and the amount of brain damage and neurological deficits caused by a stroke were significantly less in mice deficient in TLR2 or -4 compared with WT control mice. Our findings establish a proapoptotic signaling pathway for TLR2 and -4 in neurons that may render them vulnerable to ischemic death.
AB - The innate immune system senses the invasion of pathogenic microorganisms and tissue injury through Toll-like receptors (TLR), a mechanism thought to be limited to immune cells. We now report that neurons express several TLRs, and that the levels of TLR2 and -4 are increased in neurons in response to IFN-gamma stimulation and energy deprivation. Neurons from both TLR2 knockout and -4 mutant mice were protected against energy deprivation-induced cell death, which was associated with decreased activation of a proapoptotic signaling cascade involving jun N-terminal kinase and the transcription factor AP-1. TLR2 and -4 expression was increased in cerebral cortical neurons in response to ischemia/reperfusion injury, and the amount of brain damage and neurological deficits caused by a stroke were significantly less in mice deficient in TLR2 or -4 compared with WT control mice. Our findings establish a proapoptotic signaling pathway for TLR2 and -4 in neurons that may render them vulnerable to ischemic death.
M3 - SCORING: Zeitschriftenaufsatz
VL - 104
SP - 13798
EP - 13803
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 34
M1 - 34
ER -