Mena M A, Casarejos M J, Solano R, Rodríguez-Navarro J A, Gómez A, Rodal I, Medina M, de Yebenes J G
Departmento de Neurobiología-Investigación, CIBERned, Hospital Ramón y Cajal, Madrid, Spain.
FEBS Lett. 2009 Jan 5;583(1):168-74. doi: 10.1016/j.febslet.2008.11.051. Epub 2008 Dec 10.
Parkin mutations produce Parkinson's disease (PD) in humans and nigrostriatal dopamine lesions related to increased free radicals in mice. We examined the effects of NP7, a synthetic, marine derived, free radical scavenger which enters the brain, on H(2)O(2) toxicity in cultured neurons and glia from wild-type (WT) and parkin null mice (PK-KO). NP7, 5-10 microM, prevented the H(2)O(2) induced apoptosis and necrosis of midbrain neuronal and glial cultures from WT and PK-KO mice. NP7 suppressed microglial activation and the H(2)O(2) induced drop-out of dopamine neurons(.) Furthermore, NP7 prevented the increased phosphorylation of ERK and AKT induced by H(2)O(2). NP7 may be a promising neuroprotector against oxidative stress in PD.
帕金森病相关蛋白(Parkin)突变在人类中会引发帕金森病(PD),在小鼠中会导致黑质纹状体多巴胺损伤,并伴有自由基增加。我们研究了NP7(一种可进入大脑的合成海洋源自由基清除剂)对野生型(WT)和帕金森病相关蛋白基因敲除小鼠(PK-KO)原代培养神经元和神经胶质细胞中过氧化氢(H₂O₂)毒性的影响。5 - 10微摩尔的NP7可预防H₂O₂诱导的WT和PK-KO小鼠中脑神经元及神经胶质细胞培养物的凋亡和坏死。NP7可抑制小胶质细胞激活以及H₂O₂诱导的多巴胺能神经元缺失。此外,NP7可防止H₂O₂诱导的细胞外信号调节激酶(ERK)和蛋白激酶B(AKT)磷酸化增加。NP7可能是一种有前景的针对PD氧化应激的神经保护剂。