Wang Willam T, Tailor Breeya A, Cohen David S, Huang Xudong
Department of Diagnostic Radiology, Singapore General Hospital, Singapore.
Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
EC Pharmacol Toxicol. 2019 Jul;7(7):547-558. Epub 2019 Jun 21.
Alzheimer's disease (AD) characterized by insoluble amyloid-β (Aβ) deposits, neurofibrillary tangles (NFTs), and neuronal demise. The influence of environmental and genetic factors on AD progression remains elusive, however evidence suggests biometal dyshomeostasis elicits neuronal death, neuroinflammation, and accumulated oxidative damages in AD brain. As such, three pathways have been identified that result from abnormal biometal accumulation and increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in AD brain parenchyma: (1) the damage caused by direct oxidation of cellular components such as DNA and proteins; (2) the oligomerization of Aβ and NFTs, and (3) the promotion of apoptosis through NF-κB signaling pathway. Finally, given recent developments in nanotechnology, we have briefly reviewed potential nanotheranostic agents as potential AD theranostics.
阿尔茨海默病（AD）的特征是存在不溶性淀粉样β蛋白（Aβ）沉积、神经原纤维缠结（NFTs）以及神经元死亡。环境和遗传因素对AD进展的影响仍不明确，然而有证据表明生物金属稳态失衡会引发AD大脑中的神经元死亡、神经炎症以及累积的氧化损伤。因此，已确定了三条由AD脑实质中生物金属异常积累以及活性氧（ROS）和活性氮（RNS）水平升高所导致的途径：（1）细胞成分如DNA和蛋白质直接氧化造成的损伤；（2）Aβ和NFTs的寡聚化；（3）通过NF-κB信号通路促进细胞凋亡。最后，鉴于纳米技术的最新进展，我们简要回顾了作为潜在AD诊疗手段的潜在纳米诊疗剂。
