Sáez-Valero Javier, Costell Mercedes, Sjögren Magnus, Andreasen Niels, Blennow Kaj, Luque Juan M
Instituto de Neurociencias, UMH/CSIC, Campus de San Juan, San Juan, Alicante, Spain.
J Neurosci Res. 2003 Apr 1;72(1):132-6. doi: 10.1002/jnr.10554.
Reelin is an essential glycoprotein for correct cytoarchitectonic organization during CNS development. Its function in the adult brain is far less well understood, but altered brain and blood reelin levels have been reported in some psychiatric disorders, and the possibility has been considered of an involvement of the reelin signaling pathway in neurodegeneration. Here we report, for the first time, the presence of detectable levels of reelin in rat and human cerebrospinal fluid (CSF) and show evidence for the involvement of a 180-kDa reelin fragment in two neurodegenerative disorders. This fragment was analyzed by Western blotting in CSF samples from 13 healthy control individuals and 14 frontotemporal dementia (FTD) and 20 Alzheimer's disease (AD) patients. Increased CSF 180-kDa reelin was found in FTD (161.7 +/- 6.7 arbitrary units; a.u.) and AD (151.4 +/- 3.8 a.u.) compared with control individuals (141.4 +/- 1.2 a.u., P < 0.05). Our results strongly suggest the involvement of reelin signaling in neurodegenerative pathologies.
Reelin是中枢神经系统发育过程中正确细胞结构组织所必需的糖蛋白。其在成人大脑中的功能尚知之甚少,但据报道,在一些精神疾病中脑和血液中的Reelin水平会发生改变,并且人们已经考虑到Reelin信号通路参与神经退行性变的可能性。在此,我们首次报道在大鼠和人类脑脊液(CSF)中存在可检测水平的Reelin,并证明一个180 kDa的Reelin片段参与两种神经退行性疾病。通过蛋白质印迹法对13名健康对照个体以及14名额颞叶痴呆(FTD)患者和20名阿尔茨海默病(AD)患者的脑脊液样本中的该片段进行了分析。与对照个体(141.4±1.2任意单位;a.u.)相比,FTD患者(161.7±6.7任意单位;a.u.)和AD患者(151.4±3.8任意单位;a.u.)的脑脊液中180 kDa的Reelin水平升高(P<0.05)。我们的结果强烈表明Reelin信号通路参与神经退行性病变。