title: First selective dual inhibitors of tau phosphorylation and Beta-amyloid aggregation, two major pathogenic mechanisms in Alzheimer's disease.
abstract: In Alzheimer's disease (AD), multiple factors account for the accumulation of neurocellular changes, which may begin several years before symptoms appear. The most important pathogenic brain changes that are contributing to the development of AD are the formation of the cytotoxic β-amyloid aggregates and of the neurofibrillary tangles, which originate from amyloid-β peptides and hyperphosphorylated tau protein, respectively. New therapeutic agents that target both major pathogenic mechanisms may be particularly efficient. In this study, we introduce bis(hydroxyphenyl)-substituted thiophenes as a novel class of selective, dual inhibitors of the tau kinase Dyrk1A and of the amyloid-β aggregation.
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Saarland University , Saarbrücken 66123, Germany.
authors.forename: Marica
authors.initials: M
authors.lastname: Mariano
authors.forename: Christian
authors.initials: C
authors.lastname: Schmitt
authors.forename: Parisa
authors.initials: P
authors.lastname: Miralinaghi
authors.forename: Marco
authors.initials: M
authors.lastname: Catto
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
authors.forename: Angelo
authors.initials: A
authors.lastname: Carotti
authors.forename: Matthias
authors.initials: M
authors.lastname: Engel
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*; D000097603:Dyrk Kinases
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D016875:tau Proteins; D000097603:Dyrk Kinases
keywords: Alzheimer’s disease; Dyrk1A; dual inhibitors; tau protein; β-amyloid