Giunta S, Galeazzi R, Marcellini M, Corder E H, Galeazzi L
Laboratorio Analisi Chimico-Cliniche, Microbiologiche e Diagnostica Molecolare, Ospedale Geriatrico INRCA (IRCCS), via della Montagnola 81, 60100, Ancona, Italy.
Clin Biochem. 2007 Aug;40(12):887-92. doi: 10.1016/j.clinbiochem.2007.03.026. Epub 2007 Apr 20.
A neuroinflammatory process, triggered by amyloid-beta (Abeta)-peptide, is thought to play a central role in the neurodegenerative process leading to Alzheimer's disease (AD). Abeta(25-35) retains the functionality of Abeta(42) and was employed to investigate the effects of inflammation-sensitive proteins (ISPs) alpha1-antichymotrypsin (A1ACT) and alpha1-antitrypsin (A1AT) on fibrillar aggregation and cytotoxicity.
Inhibitory concentrations of the ISPs were determined in an established human red blood cell lysis model of Abeta-cytotoxicity. For studies of Abeta-fibrillar aggregation CSF levels of A1ACT (0.041 microM)/A1AT (0.11 microM) were incubated with Congo Red dye 25 microM+Abeta(25-35) 10 microM noting the formation of visible aggregates and spectrophotometric changes over 24 h.
A1ACT at CSF reported levels inhibited fibrillar aggregation and cytotoxicity while A1AT at CSF reported levels failed to cause a similar inhibition.
A1ACT neutralizes fibrillar aggregation and cytotoxicity of Abeta-peptide more effectively than A1AT. Both proteins are known to be co-deposited with Abeta within senile plaques of AD brains.
由β淀粉样蛋白（Aβ）引发的神经炎症过程被认为在导致阿尔茨海默病（AD）的神经退行性过程中起核心作用。Aβ（25 - 35）保留了Aβ（42）的功能，并被用于研究炎症敏感蛋白（ISP）α1 - 抗糜蛋白酶（A1ACT）和α1 - 抗胰蛋白酶（A1AT）对纤维状聚集和细胞毒性的影响。
在已建立的Aβ细胞毒性人红细胞裂解模型中确定ISP的抑制浓度。为了研究Aβ纤维状聚集，将脑脊液水平的A1ACT（0.041微摩尔/升）/A1AT（0.11微摩尔/升）与25微摩尔刚果红染料 + 10微摩尔Aβ（25 - 35）一起孵育，记录24小时内可见聚集体的形成和分光光度变化。
脑脊液报告水平的A1ACT抑制了纤维状聚集和细胞毒性，而脑脊液报告水平的A1AT未能产生类似的抑制作用。
A1ACT比A1AT更有效地中和Aβ肽纤维状聚集和细胞毒性。已知这两种蛋白质都与Aβ共同沉积在AD脑的老年斑中。
