Beyond secretases: Kinase inhibitors for the treatment of Alzheimer's disease

Federico Medda, Breland Smith, Vijay Gokhale, Arthur Y. Shaw, Travis Dunckley, Christopher Hulme

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)57-71
Number of pages15
JournalAnnual Reports in Medicinal Chemistry
Volume48
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Keywords

  • Alzheimer's disease
  • CDK5
  • DYRK1A
  • ERK2
  • GSK-3β
  • JNK3
  • Neurodegenerative diseases
  • Neurofibrillary tangles
  • Protein kinases
  • Tau protein

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

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