Tsuzuki K, Fukatsu R, Takamaru Y, Yoshida T, Mafune N, Kobayashi K, Fujii N, Takahata N
Department of Microbiology, Sapporo Medical University, School of Medicine, Japan.
Brain Res. 1995 Nov 20;699(2):260-5. doi: 10.1016/0006-8993(95)00917-f.
Chloroquine, a potent lysosomotropic agent, induces myopathy in experimental animals similar to rimmed vacuole (RV) myopathy in humans. The abnormal accumulation of amyloid beta protein (A beta), which is the invariable pathological alterations in the brains affected by Alzheimer's disease (AD), has been demonstrated in denervated soleus muscle fibers in chloroquine-induced myopathy in rats. In AD affected brains, a variety of additional proteins are associated with the extracellular deposition of A beta, which leads to the intracellular accumulation of neurofibrillary tangles and finally to neuronal death. In this study, we demonstrate that amyloid-associated proteins, alpha 1-antichymotrypsin, apolipoprotein E, SP-40,40 and ubiquitin co-localize with A beta in vacuolated muscle fibers in chloroquine-induced myopathy. There are striking similarities in immunopathology between experimental RV myopathy and AD. Chloroquine-induced myopathy in rats provides a suitable model not only to obtain insight into the basic mechanisms underlying RV formation in muscle, but also to understand amyloid precursor protein processing into A beta, and the role of amyloid-associated proteins in terms of the pathogenesis of AD.
氯喹是一种有效的溶酶体亲和剂，在实验动物中可诱发与人类边缘空泡（RV）肌病相似的肌病。β-淀粉样蛋白（Aβ）异常蓄积是阿尔茨海默病（AD）患者大脑中恒定的病理改变，在氯喹诱发的大鼠肌病的失神经比目鱼肌纤维中已得到证实。在AD患者大脑中，多种其他蛋白质与Aβ的细胞外沉积有关，这会导致细胞内神经原纤维缠结的蓄积，最终导致神经元死亡。在本研究中，我们证明淀粉样蛋白相关蛋白α1-抗糜蛋白酶、载脂蛋白E、SP-40,40和泛素在氯喹诱发的肌病的空泡化肌纤维中与Aβ共定位。实验性RV肌病和AD在免疫病理学上有显著相似之处。氯喹诱发的大鼠肌病不仅为深入了解肌肉中RV形成的基本机制提供了一个合适的模型，还有助于理解淀粉样前体蛋白加工成Aβ的过程，以及淀粉样蛋白相关蛋白在AD发病机制中的作用。
