Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central
nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric
ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (α2-α10)
and 3 beta (β2-β4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form
a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of
nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and
propensity to desensitize.
In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have
been found to be involved in a complex range of CNS disorders including Alzheimer’s disease (AD), Parkinson’s disease
(PD), schizophrenia, Tourette´s syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the
development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present
review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been
tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD
and age-associated memory and mild cognitive impairment.