TY - JOUR
T1 - Beyond Acetylcholinesterase Inhibitors for Treating Alzheimer's Disease
T2 - α7-nAChR Agonists in Human Clinical Trials
AU - Russo, Patrizia
AU - Bufalo, Alessandra Del
AU - Frustaci, Alessandra
AU - Fini, Massimo
AU - Cesario, Alfredo
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Alpha7-nAChR neurobiology
KW - Alpha7-nAChR role in cognition
KW - Alzheimer's disease
KW - New drugs
UR - http://www.scopus.com/inward/record.url?scp=84925875801&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925875801&partnerID=8YFLogxK
M3 - Article
C2 - 24641224
AN - SCOPUS:84925875801
VL - 20
SP - 6014
EP - 6021
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
SN - 1381-6128
IS - 38
ER -