Beyond Acetylcholinesterase Inhibitors for Treating Alzheimer's Disease: α7-nAChR Agonists in Human Clinical Trials

Patrizia Russo, Alessandra Del Bufalo, Alessandra Frustaci, Massimo Fini, Alfredo Cesario

Research output: Contribution to journalArticle

Abstract

The neuronal nicotinic alpha7-acetylcholine receptor (α7-nAChR) is a promising and attractive drug target for improving cognitive deficits in neuropsychiatric and neurological disorders such as Alzheimer's disease (AD). α7-nAChR belongs to the family of ligand gated ion channels. α7-nAChR is expressed in key brain regions (e.g. pre- and frontal cortex, hippocampus). It is involved in essential cognitive functions such as memory, thinking, comprehension, learning capacity, calculation, orientation, language, and judgment. α7-nAChR binds to amyloid peptide (Aβ) inducing either receptor activation or inhibition in an Aβ concentration-dependent mode. Aβ oligomers induce τ phosphorylation via α7-nAChR activation. α7-nAChR agonists and/or α7-nAChR positive allosteric modulators may be useful in AD therapy. The current review enlightens: (i) α7-nAChR neurobiology, (ii) α7-nAChR role in cognition and (iii) in AD, and (iv) the clinical status of the most promising molecules for the treatment of cognitive dysfunction in AD.

Original languageEnglish
Pages (from-to)6014-6021
Number of pages8
JournalCurrent Pharmaceutical Design
Volume20
Issue number38
Publication statusPublished - Jan 1 2014

Keywords

  • Alpha7-nAChR neurobiology
  • Alpha7-nAChR role in cognition
  • Alzheimer's disease
  • New drugs

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Medicine(all)

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