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Role of the α7 Nicotinic Acetylcholine Receptor and RIC-3 in the Cholinergic Anti-inflammatory Pathway

[ Vol. 17 , Issue. 2 ]

Author(s):

Treinin Millet, Papke L. Roger, Nizri Eran, Ben-David Yael, Mizrachi Tehila and Brenner Talma   Pages 90 - 99 ( 10 )

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.

Keywords:

Cholinergic anti-inflammatory pathway, α7 nicotinic acetylcholine receptor, RIC-3, multiple sclerosis, acetylcholine esterase inhibitors, metabotropic cholinergic signaling

Affiliation:

Department of Medical Neurobiology, Hebrew University - Hadassah Medical School, Jerusalem, Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Department of General Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Department of Medical Neurobiology, Hebrew University - Hadassah Medical School, Jerusalem, Department of Neurology, The Agnes Ginges Center for human Neurogenetics, Hadassah University Hospital and Hebrew University Medical School, Jerusalem, Department of Neurology, The Agnes Ginges Center for human Neurogenetics, Hadassah University Hospital and Hebrew University Medical School, Jerusalem

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