Title:Alpha7 Neuronal Nicotinic Receptor: A Pluripotent Target for Diseases of the Central Nervous System
Volume: 13
Issue: 5
Author(s): Merouane Bencherif, Sridhar T. Narla and Michal S. Stachowiak
Affiliation:
Keywords:
Alpha7 nicotinic receptor, neuroprotection, cognition, inflammation, neuroregeneration, central nervous system
diseases.
Abstract: Twenty years ago the alpha7 nicotinic acetylcholine receptor (nAChR) was thought to be vestigial with little
biological relevance, but in recent years it has emerged as a functional target with ubiquitous localization and biological
roles. In the last decade more than two thousand manuscripts have been published unraveling the multi-dimensional
complexity of this target, the heterogeneity of its genetic variants, the spectrum of transducing signals, and the critical
roles it plays in pivotal biological functions in the protection and maturation of neurons and stems cells, immune and
inflammatory responses, sensory gating, mnemonic and attentional processes. In addition research and development of
novel drugs has also promoted an intense debate on the role of activation, desensitization, β -amyloid oligomers,
glutamate, and alpha7 nAChR, in cognition, neuronal survival, and neurodegeneration. The initial alpha7 nAChRs
transducing enzyme, aptly named after Janus the two-faced roman deity for crossroads and gateways, reflects the
dichotomy of reports on alpha7 nAChRs in promoting neuronal survival and cognitive processes, or as the target of β-
amyloid oligomers to destabilize neuronal homeostasis leading to an irreversible neurochemical demise and dementia. It is
therefore important to understand the functional neural bases of alpha7 nAChRs-mediated improvement of biological
functions. The promise of alpha7 nAChR-directed drugs has already recently translated into proof-of-concept in
controlled clinical trials but the full promise of this target(s) will be fully unraveled when its impact on neuronal health
and survival is tested in controlled long-term clinical trials of disease progression.
