Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 20, Issue 38, Pages 6014-6021Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612820666140316130720
Keywords
alpha7-nAChR neurobiology; alpha7-nAChR role in cognition; Alzheimer's disease; new drugs
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The neuronal nicotinic alpha7-acetylcholine receptor (alpha 7-nAChR) is a promising and attractive drug target for improving cognitive deficits in neuropsychiatric and neurological disorders such as Alzheimer's disease (AD). alpha 7-nAChR belongs to the family of ligand gated ion channels. alpha 7-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. alpha 7-nAChR binds to amyloid peptide (A beta) inducing either receptor activation or inhibition in an A beta concentration-dependent mode. A beta oligomers induce tau phosphorylation via alpha 7-nAChR activation. alpha 7-nAChR agonists and/or alpha 7-nAChR positive allosteric modulators may be useful in AD therapy. The current review enlightens: (i) alpha 7-nAChR neurobiology, (ii) alpha 7-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.
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