Recent advances in the design, synthesis, and biological evaluation of selective DYRK1A inhibitors

A new avenue for a disease modifying treatment of Alzheimers?

Breland Smith, Federico Medda, Vijay Gokhale, Travis Dunckley, Christopher Hulme

Research output: Contribution to journalReview article

78 Citations (Scopus)

Abstract

With 24.3 million people affected in 2005 and an estimated rise to 42.3 million in 2020, dementia is currently a leading unmet medical need and costly burden on public health. Seventy percent of these cases have been attributed to Alzheimers disease (AD), a neurodegenerative pathology whose most evident symptom is a progressive decline in cognitive functions. Dual specificity tyrosine phosphorylation regulated kinase-1A (DYRK1A) is important in neuronal development and plays a variety of functional roles within the adult central nervous system. The DYRK1A gene is located within the Down syndrome critical region (DSCR) on human chromosome 21 and current research suggests that overexpression of DYRK1A may be a significant factor leading to cognitive deficits in people with Alzheimers disease (AD) and Down syndrome (DS). Currently, treatment options for cognitive deficiencies associated with Down syndrome, as well as Alzheimers disease, are extremely limited and represent a major unmet therapeutic need. Small molecule inhibition of DYRK1A activity in the brain may provide an avenue for pharmaceutical intervention of mental impairment associated with AD and other neurodegenerative diseases. We herein review the current state of the art in the development of DYRK1A inhibitors.

Original languageEnglish (US)
Pages (from-to)857-872
Number of pages16
JournalACS Chemical Neuroscience
Volume3
Issue number11
DOIs
StatePublished - Nov 21 2012
Externally publishedYes

Fingerprint

Alzheimer Disease
Down Syndrome
Neurodegenerative diseases
Neurology
Public health
Pathology
Chromosomes
Chromosomes, Human, Pair 21
Human Chromosomes
Brain
Genes
Neurodegenerative Diseases
Cognition
Dementia
Central Nervous System
Public Health
Molecules
Pharmaceutical Preparations
Research
Therapeutics

Keywords

  • Alzheimers disease
  • Down syndrome
  • DYRK1A
  • DYRK1A inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

Cite this

Recent advances in the design, synthesis, and biological evaluation of selective DYRK1A inhibitors : A new avenue for a disease modifying treatment of Alzheimers? / Smith, Breland; Medda, Federico; Gokhale, Vijay; Dunckley, Travis; Hulme, Christopher.

In: ACS Chemical Neuroscience, Vol. 3, No. 11, 21.11.2012, p. 857-872.

Research output: Contribution to journalReview article

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