In vitro effects of (+)MK-801 (dizocilpine) and memantine on β-amyloid peptides linked to Alzheimer’s Disease
| Autor: | Jing Zhao, Sudeep Banjade, Nicolina Clemente, Chunyu Wang, Ksenia Kriksunov, Susan E Coombs, Richard E. Gillilan, Robert E. Oswald |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
030302 biochemistry & molecular biology Glutamate receptor Memantine Ligand (biochemistry) Biochemistry Article Dizocilpine 03 medical and health sciences chemistry.chemical_compound Nicotinic agonist chemistry medicine Biophysics NMDA receptor Thioflavin medicine.drug Acetylcholine receptor |
| Zdroj: | Biochemistry |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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