Neuronal acetylcholine receptor alpha9-subunit: a possible central nervous system autoantigen.
Nicotinic acetylcholine receptor (AChR) is a membrane glycoprotein composed of five subunits. Muscle AChR is consist of two alpha1 and one each beta, delta, and epsilon subunits, whereas the neuronal AChR molecules are made up of various combinations of alpha (alpha2-alpha10) and beta (beta1-beta4) subunits. Myasthenia gravis (MG) develops as a result of an autoimmune attack against muscular AChR. While the prevailing symptom is muscle weakness, very rarely MG patients may develop additional central nervous system (CNS) symptoms. The majority of the anti-AChR antibodies responsible from disease induction is directed against alpha1 subunit of AChR. There is considerable identity between muscular alpha1 and neuronal alpha9 subunits. Preliminary studies showed antibodies reactive with the CNS antigens in the serum samples of mice with experimental autoimmune myasthenia gravis (EAMG). Also, alpha9 was present in the CNS in widespread locations and the binding pattern of anti-alpha9 antibody was reminiscent of that of serum samples of some of the mice with EAMG. Serum anti-AChR antibodies of myasthenic patients might be cross-reacting with CNS AChR subunits and thus inducing CNS symptoms. Neuronal AChR alpha9-subunit might be a major target antigen in this process.
Tüzün
Erdem
E
Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555-1070, USA. drerdem@yahoo.com
D000818:Animals; D001324:Autoantigens / Q000097:blood; D002490:Central Nervous System / Q000276:immunology*; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D008958:Models, Molecular; D009157:Myasthenia Gravis / Q000276:immunology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology; D009474:Neurons / Q000276:immunology; D021122:Protein Subunits / Q000276:immunology; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000276:immunology*
D001324:Autoantigens; D021122:Protein Subunits; D011950:Receptors, Cholinergic