Chapter Five - Beyond Secretases: Kinase Inhibitors for the Treatment of Alzheimer’s Disease

• Autores: Federico Medda, Breland Smith, Vijay Gokhale, Arthur Y. Shaw, Travis Dunckley, Christopher Hulme
• Localización: Annual reports in medicinal chemistry, ISSN 0065-7743, Vol 48, 2013, págs. 57-71
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Abstract Alzheimer’s disease (AD) is the most prevalent form of dementia in old age. Recent data indicate that 24.3 million people worldwide suffer from AD. Hyperphosphorylation of tau, a protein normally involved in microtubule stabilization, has been identified as an important pathological contributor to AD development. In AD brains, hyperphosphorylation of tau leads to its aggregation, misfolding, and formation of neurofibrillary tangles, one common hallmark of AD. Specific protein kinases, such as GSK-3β, CDK5, and DYRK1A, are involved in tau hyperphosphorylation and have been identified as potential targets for the development of novel therapeutic agents for the treatment of AD cognitive deficits. We herein review the current state of the art in the development of small molecule inhibitors of GSK-3β, CDK5, DYRK1A, and other protein kinases involved in tau phosphorylation. Only recently developed compounds with cellular and/or in vivo activity will be discussed.