Beyond acetylcholinesterase inhibitors for treating Alzheimer's disease: α7-nAChR agonists in human clinical trials

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

25 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)6014-6021
Numero di pagine8
RivistaCURRENT PHARMACEUTICAL DESIGN
Volume20
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • Alzheimer Disease
  • Cholinesterase Inhibitors
  • Clinical Trials as Topic
  • Drug Delivery Systems
  • Humans
  • Nicotinic Agonists
  • Treatment Outcome
  • alpha7 Nicotinic Acetylcholine Receptor

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