聚金属氧酸盐在阿尔兹海默症治疗中的新进展

doi:10.7503/cjcu20190714

摘要/Abstract

摘要：

从聚金属氧酸盐(POMs)对β-淀粉样蛋白(Aβ)聚集的调控作用、水解及光动力治疗等方面介绍其在阿尔兹海默症(AD)治疗中的最新研究进展, 为进一步研究POMs抗AD药物活性提供了参考.

Abstract:

Alzheimer’s disease(AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction and memory loss. Although the exact pathogenesis of AD remains unclear, recent evidences have demonstrated that the accumulation and deposition of β-amyloid peptide(Aβ) is a key step in AD pathogenesis. Polyoxometalates(POMs) have the merits of adjustable structures, ease of preparation, and low cost, and thus have shown promising in AD treatment. Hence, recent advances on the POMs as a novel AD metallodrug agent are summarized.

Key words: Alzheimer’s disease, Polyoxometalates, β-Amyloid

中图分类号:

O614.6

TrendMD:

马蒙蒙, 曲晓刚. 聚金属氧酸盐在阿尔兹海默症治疗中的新进展. 高等学校化学学报, 2020, 41(5): 884.

MA Mengmeng, QU Xiaogang. Recent Advances on Polyoxometalates as Metallodrug Agents for Alzheimer’s Disease ^†. Chem. J. Chinese Universities, 2020, 41(5): 884.

图/表 9

Fig.1 Schematic illustration of the Aβ-ECFP-based strategy for screening Aβ aggregation inhibitors(A)[23], Mo-POMs are capable of inhibiting Aβ aggregation and attenuating neurotoxicity(B)[25] (A) Copyright 2011, Wiley-VCH; (B) Copyright 2014, Royal Society of Chemistry.

Fig.2 Schematic representation of the high-throughput method for screening Aβ-aggregation inhibitors(A)[26] and the [CoL(H2O)]2[CoL]2[HAsVMo6VMo6VIO40] used for AD treatment(B)[27] (A) Copyright 2014, Springer Nature; (B) Copyright 2018, American Chemical Society.

Fig.4 POM@P can effectively inhibit Aβ aggregation(A)[30], schematic illustration of the peptide-modified Mo-POMs(peptide@Mo-POMs) used for AD treatment(B)[31] (A) Copyright 2013, Wiley-VCH; (B) Copyright 2019, Wiley-VCH.

Fig.5 Preparation of organic platinum-substituted POM(PtII-PW11)(A), energy minimized structures of PtII-PW11 with Aβ1—42 monomer(B) and Aβ1—42 fibril(C), in vivo evaluation of PtII-PW11 therapy(D—I)[32] Latencies for escape to platform in a spatial probe test(D), times crossing platform(E) and percentage of time spent(F) in target quadrant in a probe trial, representative swimming paths of mice with various treatments(G), immunofluorescence for Aβ1—42 depositions in the hippocampus(HIP) of WT mice, AD mice, AD mice treated with low dose(1.0 mg/mL) and high dose(1.5 mg/mL) PtII-PW11(H), percentage of senile plaques in the cortex and hippocampus(I). Copyright 2019, Wiley-VCH.

Fig.6 Chirality in different-length scales of configurational Ⅰ, conformational Ⅱ, phase Ⅲ, and object chirality Ⅳ(A), D/L-amino acid-modified POMs(B), the lowest average energy model of interaction between chiral POM and Aβ(C)[34] Copyright 2019, American Chemical Society.

Fig.7 Schematic illustration of POMs as a photosensitizer to inhibit the aggregation of Aβ upon ultraviolet(UV) light irradiation(A)[37] and rPOMDs@MSNs@copolymer as a multifunctional photothermal agent for treatment of AD(B)[38] (A) Copyright 2013, Royal Society of Chemistry; (B) Copyright 2018, Wiley-VCH.

Fig.8 Synthetic route of multifunctional nanozyme(AuNPs@POMD-8pep)(A), schematic representation of AuNPs@POMD-8pep as a multifunctional nanozyme to cure AD(B), mulliken charge distributions for the oxygen groups of POMD in the AuNPs@POMD(C)[39] Copyright 2016, Springer Nature.

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