Boggs L N, Fuson K S, Baez M, Churgay L, McClure D, Becker G, May P C
Lilly Research Laboratories, CNS Research Division, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
J Neurochem. 1996 Sep;67(3):1324-7. doi: 10.1046/j.1471-4159.1996.67031324.x.
Clusterin is a secreted glycoprotein that is markedly induced in many disease states and after tissue injury. In the CNS, clusterin expression is elevated in neuropathological conditions such as Alzheimer's disease (AD), where it is found associated with amyloid-beta (A beta) plaques. Clusterin also coprecipitates with A beta from CSF, suggesting a physiological interaction with A beta. Given this interaction with A beta, the goal of this study was to determine whether clusterin could modulate A beta neurotoxicity. A mammalian recombinant source of human clusterin was obtained by stable transfection of hamster kidney fibroblasts with pADHC-9, a full-length human cDNA clone for clusterin. Recombinant clusterin obtained from this cell line, as well as a commercial source of native clusterin purified from serum, afforded dose-dependent neuroprotection against A beta (1-40) when tested in primary rat mixed hippocampal cultures. Clusterin afforded substoichiometric neuroprotection against several lots of A beta (1-40) but not against H2O2 or kainic acid excitotoxicity. These results suggest that the elevated expression of clusterin found in AD brain may have effects on subsequent amyloid-beta plaque pathology.
簇集素是一种分泌型糖蛋白，在许多疾病状态和组织损伤后会显著诱导表达。在中枢神经系统中，簇集素在神经病理状态如阿尔茨海默病（AD）中表达升高，在那里它与β淀粉样蛋白（Aβ）斑块相关。簇集素也能与脑脊液中的Aβ共沉淀，提示其与Aβ存在生理相互作用。鉴于与Aβ的这种相互作用，本研究的目的是确定簇集素是否能调节Aβ神经毒性。通过用pADHC - 9（一种人簇集素全长cDNA克隆）稳定转染仓鼠肾成纤维细胞，获得了人簇集素的哺乳动物重组来源。从该细胞系获得的重组簇集素以及从血清中纯化的天然簇集素商业来源，在原代大鼠海马混合培养物中进行测试时，对Aβ（1 - 40）提供了剂量依赖性神经保护作用。簇集素对几批Aβ（1 - 40）提供了亚化学计量的神经保护作用，但对过氧化氢或 kainic 酸兴奋性毒性没有作用。这些结果表明，在AD脑中发现的簇集素表达升高可能对随后的β淀粉样蛋白斑块病理有影响。
