Choi-Miura N H, Oda T
Department of Physiological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Neurobiol Aging. 1996 Sep-Oct;17(5):717-22.
In the Alzheimer disease (AD) brain, senile plaques contain several proteins and cytokines, such as beta-amyloid protein (A beta), interleukin 1, transforming growth factor beta 1 (TGF beta 1), and apolipoprotein E, which may contribute to the process of neurodegeneration. Clusterin is also known to colocalize with A beta deposits in neuritic plaques. Clusterin is a multifunctional protein that causes cell aggregation, binds to beta-endorphin, and inhibits the terminal complex formation of complement. Clusterin mRNA and protein are increased in the brains of AD patients. Cytokines such as TGF beta 1 and interleukin 1 enhance the expression of clusterin, which may link clusterin to inflammatory mechanisms in AD. A beta, a 39-43 amino acid peptide, is a major component of the senile plaques that are characteristic of AD. Highly aggregated A beta is implicated in neurodegeneration, e.g., A beta aggregates spontaneously into fibrillar forms resembling those in plaques that, in experimental models, cause neurotoxicity through oxidative stress. Clusterin inhibits the aggregation of A beta, which might be neuroprotective according to the aggregation-toxicity hypothesis of A beta. However, clusterin enhanced the oxidative stress of A beta. This may extend its neurotoxicity to locations distal from plaques wherever A beta is present.
在阿尔茨海默病（AD）患者的大脑中，老年斑含有多种蛋白质和细胞因子，如β-淀粉样蛋白（Aβ）、白细胞介素1、转化生长因子β1（TGFβ1）和载脂蛋白E，这些物质可能参与神经退行性变过程。已知聚集素也与神经炎性斑中的Aβ沉积物共定位。聚集素是一种多功能蛋白质，可导致细胞聚集，与β-内啡肽结合，并抑制补体末端复合物的形成。AD患者大脑中聚集素mRNA和蛋白质水平升高。诸如TGFβ1和白细胞介素1等细胞因子可增强聚集素的表达，这可能将聚集素与AD中的炎症机制联系起来。Aβ是一种由39 - 43个氨基酸组成的肽，是AD特征性老年斑的主要成分。高度聚集的Aβ与神经退行性变有关，例如，Aβ可自发聚集成类似斑块中的纤维状形式，在实验模型中，通过氧化应激导致神经毒性。根据Aβ的聚集 - 毒性假说，聚集素可抑制Aβ的聚集，这可能具有神经保护作用。然而，聚集素会增强Aβ的氧化应激。这可能会将其神经毒性扩展到Aβ存在的斑块远端位置。
