title: Cholinergic System and Neuroinflammation: Implication in Multiple Sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) characterized by leucocytes infiltration, demyelination, axonal degeneration and neuronal death. Although the etiology of MS is still unkwon, inflammation and autoimmunity are considered to be key players of the disease. Nervous System: The severe alterations affecting the nervous system contribute to the motor and cognitive disabilities and are in large part dependent on severe inflammatory processes active in both central nervous system and immune system. Acetylcholine (ACh) appears to be involved in the modulation of central and peripheral inflammation. Immune cells as well as astrocytes and microglia respond to ACh stimuli by activation of cholinergic receptors. Muscarinic and nicotinic receptors differently contribute to the modulation of immunological and inflammatory processes stimulating pro- and anti-inflammatory cytokines respectively. The role played by ACh in MS is not yet fully understood, although some results point to its involvement in different neurological disorders such as Alzheimer's disease and schizophrenia.
  
  
  CONCLUSIONS
  In the present review we summarize the evidence indicating the correlation between nervous system dysfunction in MS, with inflammation and cholinergic system alterations. Experiments performed in MS animal models and analyses on biological fluids from MS patients such as blood, serum and cerebrospinal fluid suggest that cholinergic alterations may contribute to the dysregulated inflammatory processes of MS. Many current therapeutic approaches in MS are based on anti-inflammatory drugs. We also discuss how the use of cholinesterase inhibitors or ACh mimetics may represent a new interesting therapeutic approach in MS.
authors.affiliation: Department of Biology and Biotechnologies C. Darwin, Research Center of Neurobiology Daniel Bovet, "Sapienza" University of Rome, Italy.|IIBB-CSIC, IDIBAPS, CIBERNED, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bari
authors.affiliation: Department of Biology and Biotechnologies C. Darwin, Research Center of Neurobiology Daniel Bovet, "Sapienza" University of Rome, Italy.|IIBB-CSIC, IDIBAPS, CIBERNED, Barcelona, Spain.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Pinto
authors.affiliation: Department of Medical, Oral and Biotechnological Science, University "G. d'Annunzio" Chieti-Pescara, Pescara, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Reale
authors.affiliation: IIBB-CSIC, IDIBAPS, CIBERNED, Rosselló 161, Barcelona, Spain.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Mengod
authors.affiliation: Department of Biology and Biotechnologies C. Darwin, Research Center of Neurobiology Daniel Bovet, "Sapienza" University of Rome, Italy.
authors.forename: Ada Maria
authors.initials: AM
authors.lastname: Tata
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018678:Cholinergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D018836:Inflammation Mediators
keywords: Acetylcholine; cholinergic markers; inflammation; multiple sclerosis; muscarinic receptors; nicotinic receptors