Title:Role of the α7 Nicotinic Acetylcholine Receptor and RIC-3 in the Cholinergic Anti-inflammatory Pathway
Volume: 17
Issue: 2
Author(s): Treinin M, Papke RL, Nizri E, Ben-David Y, Mizrachi T and Brenner T*
Affiliation:
- Department of Neurology, The Agnes Ginges Center for human Neurogenetics, Hadassah University Hospital and Hebrew University Medical School, Jerusalem,Israel
Keywords:
Cholinergic anti-inflammatory pathway, α7 nicotinic acetylcholine receptor, RIC-3, multiple sclerosis, acetylcholine
esterase inhibitors, metabotropic cholinergic signaling
Abstract: Background: The nicotinic acetylcholine receptor (nAChR) gene family encodes for
subunits of acetylcholine gated ion channels. These receptors are expressed widely and have many
functions: They mediate excitation at neuro-muscular junctions.
Nicotinic Acetylcholine Receptor: In the central nervous system nAChRs have been implicated in
memory, cognition, and addiction. And in non-excitatory cells they regulate differentiation, proliferation
and inflammatory responses. The CHRNA7 gene encodes for the α7 nAChR subunit that assembles
into a homomeric receptor having unusual properties. It is expressed widely and has many functions
atypical for nAChRs; specifically, in immune cells α7 is required for the anti-inflammatory effects
of acetylcholine and has been implicated in inflammatory autoimmune diseases including Multiple
Sclerosis (MS). Interestingly, although, α7 receptors are found at the outer membranes of immune
cells, acetylcholine-dependent currents have not been recorded from these cells. Therefore, its mechanism
of action in immune cells needs further evaluation. Maturation of α7 into functional ligand-gated
channels in the plasma membrane is a complex process shown to depend on the ER-resident chaperone,
RIC-3. Therefore, RIC-3 regulates functional expression of α7. RIC-3 like α7 is expressed in
immune cells and has been implicated in MS. Thus, RIC-3 may regulate functional expression of α7
in immune cells.
Conclusion: In this review we describe effects and mechanism of action of α7 nAChR and RIC-3 in
the immune cholinergic system. Elucidating these mechanisms and the regulation of α7 and RIC-3 in
the immune cholinergic system can pave the way for novel immunomodulatory agents, or towards extending
the application of cholinergic agents.
