title: Beyond acetylcholinesterase inhibitors for treating Alzheimer's disease: α7-nAChR agonists in human clinical trials.
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.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Russo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Del Bufalo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Frustaci
authors.forename: Massimo
authors.initials: M
authors.lastname: Fini
authors.affiliation: Laboratory of Systems Approaches and Non Communicable Diseases, IRCCS "San Raffaele Pisana", Via di Valcannuta, 247, I-00166 Roma, Italia. patrizia_russo@hotmail.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cesario
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000453:epidemiology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D002986:Clinical Trials as Topic / Q000639:trends; D016503:Drug Delivery Systems / Q000639:trends; D006801:Humans; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D016896:Treatment Outcome; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: D002800:Cholinesterase Inhibitors; D018722:Nicotinic Agonists; D064569:alpha7 Nicotinic Acetylcholine Receptor