Neuronal acetylcholine receptor α9-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 α1 and one each β, δ, and ε subunits, whereas the neuronal AChR molecules are made up of various combinations of α (α2-α10) and β (β1-β4) 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 α1 subunit of AChR. There is considerable identity between muscular α1 and neuronal α9 subunits. Preliminary studies showed antibodies reactive with the CNS antigens in the serum samples of mice with experimental autoimmune myasthenia gravis (EAMG). Also, α9 was present in the CNS in widespread locations and the binding pattern of anti-α9 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 α9-subunit might be a major target antigen in this process.