Ma Mengmeng, Liu Zhenqi, Zhao Huisi, Zhang Haochen, Ren Jinsong, Qu Xiaogang
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China.
Natl Sci Rev. 2024 Jun 28;11(7):nwae226. doi: 10.1093/nsr/nwae226. eCollection 2024 Jul.
Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects ∼50 million people globally. The accumulation of amyloid-β (Aβ) plaques, a predominant pathological feature of AD, plays a crucial role in AD pathogenesis. In this respect, Aβ has been regarded as a highly promising therapeutic target for AD treatment. Polyoxometalates (POMs) are a novel class of metallodrugs being developed as modulators of Aβ aggregation, owing to their negative charge, polarity, and three-dimensional structure. Unlike traditional discrete inorganic complexes, POMs contain tens to hundreds of metal atoms, showcasing remarkable tunability and diversity in nuclearities, sizes, and shapes. The easily adjustable and structurally variable nature of POMs allows for their favorable interactions with Aβ. This mini-review presents a balanced overview of recent progress in using POMs to mitigate amyloidosis. Clear correlations between anti-amyloid activities and structural features of POMs are also elaborated in detail. Finally, we discuss the current challenges and future prospects of POMs in combating AD.
阿尔茨海默病（AD）是一种毁灭性的神经退行性疾病，全球约有5000万人受其影响。淀粉样β蛋白（Aβ）斑块的积累是AD的主要病理特征，在AD发病机制中起着关键作用。在这方面，Aβ被认为是AD治疗中极具前景的治疗靶点。多金属氧酸盐（POMs）是一类新型金属药物，由于其负电荷、极性和三维结构，正被开发用作Aβ聚集的调节剂。与传统的离散无机配合物不同，POMs包含数十到数百个金属原子，在核数、尺寸和形状方面展现出显著的可调性和多样性。POMs易于调节且结构可变的性质使其能够与Aβ产生良好的相互作用。这篇小型综述全面概述了使用POMs减轻淀粉样变性的最新进展。还详细阐述了POMs的抗淀粉样活性与结构特征之间的明确关联。最后，我们讨论了POMs在对抗AD方面当前面临的挑战和未来前景。
