Alpha7 nicotinic receptors as novel therapeutic targets for inflammation-based diseases.
In recent years the etiopathology of a number of debilitating diseases such as type 2 diabetes, arthritis, atherosclerosis, psoriasis, asthma, cystic fibrosis, sepsis, and ulcerative colitis has increasingly been linked to runaway cytokine-mediated inflammation. Cytokine-based therapeutic agents play a major role in the treatment of these diseases. However, the temporospatial changes in various cytokines are still poorly understood and attempts to date have focused on the inhibition of specific cytokines such as TNF-α. As an alternative approach, a number of preclinical studies have confirmed the therapeutic potential of targeting alpha7 nicotinic acetylcholine receptor-mediated anti-inflammatory effects through modulation of proinflammatory cytokines. This "cholinergic anti-inflammatory pathway" modulates the immune system through cholinergic mechanisms that act on alpha7 receptors expressed on macrophages and immune cells. If the preclinical findings translate into human efficacy this approach could potentially provide new therapies for treating a broad array of intractable diseases and conditions with inflammatory components.
Bencherif
Merouane
M
Preclinical Research, Targacept, Inc., Winston-Salem, NC 27101, USA. Merouane.Bencherif@Targacept.com
Lippiello
Patrick M
PM
Lucas
Rudolf
R
Marrero
Mario B
MB
D001168:Arthritis / Q000150:complications; D001249:Asthma / Q000150:complications; D003093:Colitis, Ulcerative / Q000150:complications; D003550:Cystic Fibrosis / Q000150:complications; D016207:Cytokines / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000737:chemistry / Q000378:metabolism*; D010300:Parkinson Disease / Q000150:complications; D011565:Psoriasis / Q000150:complications; D011978:Receptors, Nicotinic / Q000378:metabolism*; D018805:Sepsis / Q000150:complications; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D016207:Cytokines; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor