Neuronal acetylcholine receptor alpha 9-subunit: A possible central nervous system autoantigen

Abstract

Nicotinic acetylcholine receptor (AChR) is a membrane glycoprotein composed of five subunits. Muscle AChR is consist of two alpha 1 and one each beta, delta, and epsilon subunits, whereas the neuronal AChR molecules are made up of various combinations of alpha (alpha 2-alpha 10) and beta (beta 1-beta 4) 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 alpha 1 subunit of AChR. There is considerable identity between muscular alpha 1 and neuronal alpha 9 subunits. Preliminary studies showed antibodies reactive with the CNS antigens in the serum samples of mice with experimental autoimmune myasthenia gravis (EAMG). Also, alpha 9 was present in the CNS in widespread locations and the binding pattern of anti-alpha 9 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 alpha 9-subunit might be a major target antigen in this process. (c) 2006 Elsevier Ltd. All rights reserved.