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

Author(s): Treinin M, Papke RL, Nizri E, Ben-David Y, Mizrachi T, Brenner T*.

Journal Name: Central Nervous System Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

Volume 17 , Issue 2 , 2017

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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

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Article Details

VOLUME: 17
ISSUE: 2
Year: 2017
Page: [90 - 99]
Pages: 10
DOI: 10.2174/1871524916666160829114533
Price: $58

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