title: Role of the α7 Nicotinic Acetylcholine Receptor and RIC-3 in the Cholinergic Anti-inflammatory Pathway.
abstract: 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.
  
  
  
  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.
authors: Department of Medical Neurobiology, Hebrew University - Hadassah Medical School, Jerusalem, Israel.
authors: Millet
authors: M
authors: Treinin
authors: Department of Pharmacology and Therapeutics, University of Florida, Gainesville, United States.
authors: Roger L
authors: RL
authors: Papke
authors: Department of General Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors: Eran
authors: E
authors: Nizri
authors: Department of Medical Neurobiology, Hebrew University - Hadassah Medical School, Jerusalem, Israel.
authors: Yael
authors: Ben-David
authors: Department of Neurology, The Agnes Ginges Center for human Neurogenetics, Hadassah University Hospital and Hebrew University Medical School, Jerusalem, Israel.
authors: Tehila
authors: T
authors: Mizrachi
authors: Department of Neurology, The Agnes Ginges Center for human Neurogenetics, Hadassah University Hospital and Hebrew University Medical School, Jerusalem, Israel.
authors: Talma
authors: T
authors: Brenner
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018678:Cholinergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000502:physiology*
chemical_list: D000893:Anti-Inflammatory Agents; D018678:Cholinergic Agents; D007155:Immunologic Factors; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; C496701:RIC3 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Cholinergic anti-inflammatory pathway; RIC-3; acetylcholine
  esterase inhibitors; metabotropic cholinergic signaling; multiple sclerosis; α7 nicotinic acetylcholine receptor