摘要:β-淀粉样蛋白(Amyloid-ββ,Aβ)是阿尔茨海默症(Alzheimer's disease,AD)病人大脑中淀粉样斑块的主要组成部分.β-淀粉样蛋白级联假说指出,Aβ在脑实质的沉积是最终导致阿尔茨海默症的一个关键步骤.目前的大量研究表明,相对于高度聚集的Aβ,可溶性的Aβ低聚物可能与认知功能障碍的关联性更强.血红素(heme)的代谢在AD患者大脑中发生了改变.近来发现heme可与Aβ结合,形成一个复合物Aβ-heme,该复合物拥有显著高于heme的过氧化物酶活性,具有比heme更强的催化蛋白质酪氨酸硝化的能力.这个结果提示,Aβ-heme可能是联系Aβ与AD中大量蛋白质发生硝化的关键分子.同时,Aβ与heme的结合改变了heme催化蛋白质硝化的位点选择性.这些研究对于阐明Aβ和heme在体内可能的生理作用具有重要意义.%Amyloid-P (Aβ) is the major component of amyloid plaques in Alzheimer's disease (AD). Aβ cascade hypothesis suggested that Aβ deposition in the brain substance is a critical step which eventually leads to Alzheimer's disease. A large number of studies have shown that soluble Aβ oligomers are more toxic than Ap aggregates and may be associated with cognitive dysfunction. The metabolism of heme was found to be changed in the brain of AD patients. Meanwhile, Ap was found to bind to heme, forming Aβ-heme complex, which might contributed to the alteration of heme homeostasis in AD. The binding of heme to Aβ can inhibit Ap aggregation and also can dissociate the aggregated state of Aβ, indicating that the interaction of Aβ with heme can play an important role in AD. Interestingly, Ap-heme complex was found to possess higher peroxidase activity than heme, and we found this complex was more effective than heme in catalyzing the nitration of proteins, which imply that Ap-heme may be the molecular link between Ap and the widespread protein nitration in AD. Moreover, Aβ binds to heme has been shown to change the selectivity of the heme catalyzed protein nitration. These studies would help to understand the physiological roles of Ap-heme in vivo and may be helpful for AD prevention and treatment.
展开▼
