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In silico evidence of direct interaction between statins and β-amyloid

dc.contributor.authorShakour N.
dc.contributor.authorBianconi V.
dc.contributor.authorPirro M.
dc.contributor.authorBarreto G.E.
dc.contributor.authorHadizadeh F.
dc.contributor.authorSahebkar A.
dc.date.accessioned2020-09-02T22:28:12Z
dc.date.available2020-09-02T22:28:12Z
dc.date.issued2019
dc.identifier10.1002/jcb.27761
dc.identifier.citation120, 3, 4710-4715
dc.identifier.issn07302312
dc.identifier.urihttps://hdl.handle.net/20.500.12728/6241
dc.descriptionIntroduction: Aggregation of amyloid-β (Aβ) peptides represents a crucial step in the pathogenesis of Alzheimer disease (AD). Compelling evidence from preclinical studies has established that statins may reduce amyloidogenesis and Aβ-mediated neurodegeneration, supporting a potential role of statin treatment in the prevention of AD. Different statins have been shown to interfere indirectly with Aβ production and clearance through either cholesterol-dependent or cholesterol-independent mechanisms. However, whether there may be a direct interaction between statins and Aβ metabolism is still unclear. Materials and methods: To test the possible direct interaction between statins and Aβ, we performed an in silico study by testing the orientation of different ligands, including statins and sulindac (the standard ligand of Aβ), in the Aβ active site using molecular operating environment (MOE) software. Results: Docking experiments showed that all the tested statins could directly interact with Aβ protofibrils. Among statins, pitavastatin had the strongest interaction with Aβ (pk i = 7.66), followed by atorvastatin (pk i = 7.63), rosuvastatin (pk i = 6.99), fluvastatin (pk i = 6.96), pravastatin (pk i = 6.46), lovastatin (pk i = 6.37), and simvastatin (pk i = 5.90). According to the above-mentioned results, pitavastatin, atorvastatin, rosuvastatin, and fluvastatin had a stronger binding to Aβ compared with the standard ligand sulindac (pk i = 6.62). Conclusion: This study showed a direct interaction between statins and Aβ protofibrils, which may underlie the protective role of this widely used class of drugs against amyloidogenesis and Aβ-mediated neurodegeneration. © 2018 Wiley Periodicals, Inc.
dc.language.isoen
dc.publisherWiley-Liss Inc.
dc.subjectAlzheimer's disease (AD)
dc.subjectamyloid-β (Aβ)
dc.subjectdocking
dc.subjectstatins
dc.subjectamyloid beta protein
dc.subjectatorvastatin
dc.subjectfluindostatin
dc.subjecthydroxymethylglutaryl coenzyme A reductase inhibitor
dc.subjectmevinolin
dc.subjectpitavastatin
dc.subjectpravastatin
dc.subjectrosuvastatin
dc.subjectsimvastatin
dc.subjectsulindac
dc.subjectamyloid beta protein
dc.subjecthydroxymethylglutaryl coenzyme A reductase inhibitor
dc.subjectArticle
dc.subjectcomputer model
dc.subjectcontrolled study
dc.subjectcrystal structure
dc.subjectdrug protein binding
dc.subjectenzyme active site
dc.subjectmolecular docking
dc.subjectmolecular operating environment software
dc.subjectpriority journal
dc.subjectprotein metabolism
dc.subjectsoftware
dc.subjectAlzheimer disease
dc.subjectchemistry
dc.subjecthuman
dc.subjectmetabolism
dc.subjectmolecular docking
dc.subjectpathology
dc.subjectAlzheimer Disease
dc.subjectAmyloid beta-Peptides
dc.subjectCatalytic Domain
dc.subjectHumans
dc.subjectHydroxymethylglutaryl-CoA Reductase Inhibitors
dc.subjectMolecular Docking Simulation
dc.titleIn silico evidence of direct interaction between statins and β-amyloid
dc.typeArticle


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