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

[ Vol. 20 , Issue. 38 ]

Author(s):

Patrizia Russo, Alessandra Del Bufalo, Alessandra Frustaci, Massimo Fini and Alfredo Cesario   Pages 6014 - 6021 ( 8 )

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 A β concentration-dependent mode. A β 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.

Keywords:

alpha7-nAChR neurobiology, alpha7-nAChR role in cognition, Alzheimer's disease, new drugs.

Affiliation:

, , , , Laboratory of Systems Approaches and Non Communicable Diseases, IRCCS "San Raffaele Pisana", Via di Valcannuta, 247, I-00166 Roma, Italia.



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