The role of AQP4 in neuromyelitis optica: More answers, more questions

• This review summarizes current thinking about the role of NMO-IgG in the pathogenesis of this condition.
• Complement-dependent cytotoxicity is probably the major mechanism.
• Disturbance of potassium, glutamate and cell-volume regulation might also play a role in the mechanism.

Neuromyelitis optica (NMO) is a recurrent inflammatory disease that preferentially targets the optic nerves and spinal cord. The presence of antibodies to the water channel protein aquaporin-4 (AQP4), expressed almost exclusively in astrocytes in the central nervous system (CNS), is a reliable biomarker for NMO. These antibodies, NMO-IgG, may be responsible for the sequential cascade of immune events, including IgG/IgM deposition, infiltration of granulocytes and complement-mediated cytotoxicity (i.e. astrocyte loss) and demyelination. This review summarizes current thinking about the role of NMO-IgG in the pathogenesis of this condition. New insights were also generated along with important additional questions.