First Selective Dual Inhibitors of Tau Phosphorylation and Beta-Amyloid Aggregation, Two Major Pathogenic Mechanisms in Alzheimer’s Disease

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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.
Funding Information
  • Deutsche Forschungsgemeinschaft (EN 381/3-1)

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