Mutsuga Mayu, Chambers James Kenn, Uchida Kazuyuki, Tei Meina, Makibuchi Takao, Mizorogi Tatsuya, Takashima Akihiko, Nakayama Hiroyuki
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
J Vet Med Sci. 2012 Jan;74(1):51-7. doi: 10.1292/jvms.11-0307. Epub 2011 Sep 2.
The binding of curcumin to senile plaques (SPs) and cerebral amyloid angiopathy (CAA) was examined in the aged brain of various animal species and a human patient with Alzheimer's disease (AD), together with its binding to neurofibrillary tangles (NFTs). Brain sections were immunostained with anti-amyloid β protein 1-42 (Aβ42) and anti-amyloid β protein 1-40 (Aβ40) antibodies. These sections were also stained with alkaline Congo red, periodic acid-methenamine silver (PAM), and curcumin (0.009% curcumin solution) with or without formic acid pretreatment. The sections from the AD brain were also immunostained for anti-paired helical filament-tau (PHF-tau), and were stained with Gallyas silver for NFTs. Some SPs in the AD, monkey, dog, bear, and amyloid precursor protein transgenic mouse (APP Tg-mouse) brains contained congophilic materials, and were intensely positive for curcumin. In addition, curcumin labeled some diffuse SPs negative for Congo red in the AD, monkey, bear, and APP Tg-mouse brains. In all animals, CAA was intensely positive for both Congo red and curcumin. The specific curcumin staining activity was lost by formic acid pretreatment. In the AD brain, NFTs positive for PHF-tau and Gallyas silver were moderately stained with curcumin. These findings indicate that curcumin specifically binds to the aggregated Aβ molecules in various animals, and further to phosphorylated tau protein, probably according to its conformational nature.
在多种动物物种的老年大脑以及一名阿尔茨海默病(AD)人类患者的大脑中,研究了姜黄素与老年斑(SPs)和脑淀粉样血管病(CAA)的结合情况,以及其与神经原纤维缠结(NFTs)的结合情况。用脑切片进行免疫染色,使用抗淀粉样β蛋白1 - 42(Aβ42)和抗淀粉样β蛋白1 - 40(Aβ40)抗体。这些切片还用碱性刚果红、高碘酸 - 亚甲胺银(PAM)以及姜黄素(0.009%姜黄素溶液)进行染色,其中姜黄素染色有的进行了甲酸预处理,有的未进行。来自AD大脑的切片还进行了抗双螺旋丝 - tau(PHF - tau)免疫染色,并用Gallyas银染法对NFTs进行染色。AD、猴子、狗、熊以及淀粉样前体蛋白转基因小鼠(APP Tg - 小鼠)大脑中的一些SPs含有嗜刚果红物质,并且对姜黄素呈强阳性。此外,姜黄素标记了AD、猴子、熊和APP Tg - 小鼠大脑中一些刚果红阴性的弥漫性SPs。在所有动物中,CAA对刚果红和姜黄素均呈强阳性。甲酸预处理会使姜黄素的特异性染色活性丧失。在AD大脑中,PHF - tau和Gallyas银染阳性的NFTs被姜黄素适度染色。这些发现表明,姜黄素能特异性地与各种动物中聚集的Aβ分子结合,并且可能根据其构象性质进一步与磷酸化的tau蛋白结合。