Arumugam Thiruma V, Chan Sic L, Jo Dong-Gyu, Yilmaz Gokhan, Tang Sung-Chun, Cheng Aiwu, Gleichmann Marc, Okun Eitan, Dixit Vishwa D, Chigurupati Srinivasulu, Mughal Mohamed R, Ouyang Xin, Miele Lucio, Magnus Tim, Poosala Suresh, Granger D Neil, Mattson Mark P
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
Nat Med. 2006 Jun;12(6):621-3. doi: 10.1038/nm1403. Epub 2006 May 7.
Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme gamma-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apoptosis, and by activating microglial cells and stimulating the infiltration of proinflammatory leukocytes. These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions.
在局灶性缺血性中风模型中，转反义Notch基因的小鼠以及用Notch激活酶γ-分泌酶抑制剂处理的正常小鼠，其脑细胞损伤减轻，功能结局得到改善。Notch通过调节增加神经元对凋亡易感性的信号通路，以及激活小胶质细胞和刺激促炎白细胞浸润来危及神经元。这些发现表明，Notch信号通路可能是治疗中风及相关神经退行性疾病的一个治疗靶点。
