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

详细信息    查看全文

• 作者：Marica Mariano ; Christian Schmitt ; Parisa Miralinaghi ; Marco Catto ; Rolf W. Hartmann ; Angelo Carotti ; Matthias Engel
• 刊名：ACS Chemical Neuroscience
• 出版年：2014
• 出版时间：December 17, 2014
• 年：2014
• 卷：5
• 期：12
• 页码：1198-1202
• 全文大小：207K
• ISSN：1948-7193

文摘

In Alzheimer鈥檚 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 尾-amyloid aggregates and of the neurofibrillary tangles, which originate from amyloid-尾 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-尾 aggregation.

Keywords:

Alzheimer鈥檚 disease; 尾-amyloid; tau protein; Dyrk1A; dual inhibitors