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In Vitro Effects of (+)MK-801 (dizocilpine) and Memantine on β-Amyloid Peptides Linked to Alzheimer’s Disease
Biochemistry ( IF 2.9 ) Pub Date : 2020-11-29 , DOI: 10.1021/acs.biochem.0c00813 Susan E. Coombs , Sudeep Banjade , Ksenia Kriksunov , Nicolina Clemente 1 , Jing Zhao 1 , Chunyu Wang 1 , Richard E. Gillilan , Robert E. Oswald
Biochemistry ( IF 2.9 ) Pub Date : 2020-11-29 , DOI: 10.1021/acs.biochem.0c00813 Susan E. Coombs , Sudeep Banjade , Ksenia Kriksunov , Nicolina Clemente 1 , Jing Zhao 1 , Chunyu Wang 1 , Richard E. Gillilan , Robert E. Oswald
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An in vitro effect of (+)MK-801 (dizocilpine), an inhibitor of the glutamate/NMDA and nicotinic acetylcholine receptors, on the Aβ[1–42] and Aβ[1–40] peptides is described and compared to that of memantine. Memantine has been approved by the U.S. Food and Drug Administration for the treatment of mild-moderate Alzheimer’s disease. Both compounds accelerated the formation of a β-sheet structure by Aβ[1–42], (+)MK-801 more rapidly than memantine, as observed in a thioflavin T fluorescence assay. The acceleration was followed by a decrease in the fluorescence signal that was not observed when the ligand was absent. Nuclear magnetic resonance spectra of the soluble peptides in the presence and absence of (+)MK-801 demonstrated that the monomeric form did not bind (+)MK-801 and that in the presence of (+)MK-801 the concentration of the monomeric form progressively decreased. Small angle X-ray scattering confirmed that the presence of (+)MK-801 resulted in a more rapid and characteristic transition to an insoluble form. These results suggest that (+)MK-801 and memantine accelerate the transition of Aβ[1–42] and Aβ[1–40] to ThT-negative insoluble forms.
中文翻译：
（+）MK-801（二唑西平）和美金刚胺对与阿尔茨海默氏病有关的β-淀粉样肽的体外作用
一种在体外描述了谷氨酸/ NMDA和烟碱乙酰胆碱受体抑制剂（+）MK-801（地佐西平）对Aβ[1-42]和Aβ[1-440]肽的作用，并与美金刚进行了比较。美金刚已被美国食品和药物管理局批准用于治疗轻度中度阿尔茨海默氏病。如硫代黄素T荧光测定法所观察到的，这两种化合物都比美金刚更快地促进了Aβ[1-42]（+）MK-801通过β-折叠结构的形成。加速之后是荧光信号的下降，当缺乏配体时未观察到。在存在和不存在（+）MK-801的情况下可溶性肽的核磁共振谱表明，单体形式不与（+）MK-801结合，而在存在（+）MK-801的情况下，单体形式逐渐减少。小角度X射线散射证实（+）MK-801的存在导致了更快，更特征性的转变为不溶形式。这些结果表明，（+）MK-801和美金刚促进了Aβ[1-42]和Aβ[1-4]向ThT阴性不溶形式的转变。
更新日期：2020-12-08
中文翻译：
（+）MK-801（二唑西平）和美金刚胺对与阿尔茨海默氏病有关的β-淀粉样肽的体外作用
一种在体外描述了谷氨酸/ NMDA和烟碱乙酰胆碱受体抑制剂（+）MK-801（地佐西平）对Aβ[1-42]和Aβ[1-440]肽的作用，并与美金刚进行了比较。美金刚已被美国食品和药物管理局批准用于治疗轻度中度阿尔茨海默氏病。如硫代黄素T荧光测定法所观察到的，这两种化合物都比美金刚更快地促进了Aβ[1-42]（+）MK-801通过β-折叠结构的形成。加速之后是荧光信号的下降，当缺乏配体时未观察到。在存在和不存在（+）MK-801的情况下可溶性肽的核磁共振谱表明，单体形式不与（+）MK-801结合，而在存在（+）MK-801的情况下，单体形式逐渐减少。小角度X射线散射证实（+）MK-801的存在导致了更快，更特征性的转变为不溶形式。这些结果表明，（+）MK-801和美金刚促进了Aβ[1-42]和Aβ[1-4]向ThT阴性不溶形式的转变。
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