TY - JOUR
T1 - Anti-inflammatory properties of cholinergic up-regulation
T2 - A new role for acetylcholinesterase inhibitors
AU - Nizri, Eran
AU - Hamra-Amitay, Yasmine
AU - Sicsic, Camille
AU - Lavon, Iris
AU - Brenner, Talma
N1 - Funding Information:
This research was supported by grants from the Association Français contre les Myopathies (AFM) and Ester Neuroscience. We thank Drs. D. Karussis and M. Weinstock-Rosin for helpful discussions, and Mrs. F. Pinto–Maravi and Mrs. D. Fuchs for their excellent technical assistance.
PY - 2006/4
Y1 - 2006/4
N2 - We investigated the anti-inflammatory effects of acetylcholinesterase inhibitors (AChEI) at the cellular and molecular levels. AChEI suppressed lymphocyte proliferation and pro-inflammatory cytokine production, as well as extracellular esterase activity. Anti-inflammatory activity was mediated by the α7 nicotinic acetylcholine receptor (neuronal); the muscarinic receptor had the opposite effect. Treatment of the central nervous system (CNS) inflammatory disease, experimental autoimmune encephalomyelitis (EAE), with EN101, an anti-sense oligodeoxynucleotide, targeted to AChE mRNA, reduced the clinical severity of the disease and CNS inflammation intensity. The results of our experiments suggest that AChEI increase the concentration of extracellular acetylcholine (ACh), rendering it available for interaction with a nicotinic receptor expressed on lymphocytes. Our findings point to a novel role for AChEI which may be relevant in CNS inflammatory diseases such as EAE and multiple sclerosis. They also emphasize the importance of cholinergic balance in neurological disorders, such as Alzheimer's disease and myasthenia gravis, in which these drugs are used.
AB - We investigated the anti-inflammatory effects of acetylcholinesterase inhibitors (AChEI) at the cellular and molecular levels. AChEI suppressed lymphocyte proliferation and pro-inflammatory cytokine production, as well as extracellular esterase activity. Anti-inflammatory activity was mediated by the α7 nicotinic acetylcholine receptor (neuronal); the muscarinic receptor had the opposite effect. Treatment of the central nervous system (CNS) inflammatory disease, experimental autoimmune encephalomyelitis (EAE), with EN101, an anti-sense oligodeoxynucleotide, targeted to AChE mRNA, reduced the clinical severity of the disease and CNS inflammation intensity. The results of our experiments suggest that AChEI increase the concentration of extracellular acetylcholine (ACh), rendering it available for interaction with a nicotinic receptor expressed on lymphocytes. Our findings point to a novel role for AChEI which may be relevant in CNS inflammatory diseases such as EAE and multiple sclerosis. They also emphasize the importance of cholinergic balance in neurological disorders, such as Alzheimer's disease and myasthenia gravis, in which these drugs are used.
KW - Acetylcholinesterase
KW - Acetylcholinesterase inhibitors
KW - Alzheimer's disease
KW - CNS inflammation
KW - Experimental autoimmune encephalomyelitis
KW - α7 Nicotinic receptor
UR - http://www.scopus.com/inward/record.url?scp=33645237919&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2005.10.013
DO - 10.1016/j.neuropharm.2005.10.013
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C2 - 16336980
AN - SCOPUS:33645237919
SN - 0028-3908
VL - 50
SP - 540
EP - 547
JO - Neuropharmacology
JF - Neuropharmacology
IS - 5
ER -
