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

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.

Cite this article as:

M Treinin , RL Papke, E Nizri, Y Ben-David, T Mizrachi and T Brenner*, Role of the α7 Nicotinic Acetylcholine Receptor and RIC-3 in the Cholinergic Anti-inflammatory Pathway, Central Nervous System Agents in Medicinal Chemistry 2017; 17 (2) . https://dx.doi.org/10.2174/1871524916666160829114533

DOI https://dx.doi.org/10.2174/1871524916666160829114533	Print ISSN 1871-5249
Publisher Name Bentham Science Publisher	Online ISSN 1875-6166