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Molecular Pathogenesis of Neuromyelitis Optica
School of Medicine, Gold Coast Campus, Griffith University, QLD 4222, Australia
Department of Neurology, Gold Coast Hospital, Southport, QLD 4215, Australia
Brain and Mind Research Institute, Camperdown, NSW 2050, Australia
Autoimmune laboratory, Division of Immunology, Pathology Queensland, Herston, QLD 4029, Australia
* Author to whom correspondence should be addressed.
Received: 3 August 2012; in revised form: 8 September 2012 / Accepted: 13 September 2012 / Published: 11 October 2012
Abstract: Neuromyelitis optica (NMO) is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG) against aquaporin-4 (AQP4), a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS) when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6) have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies.
Keywords: pathogenesis; Devic’s disease; immunology; genetics; neuromyelitis optica; multiple sclerosis; aquaporin-4; astrocytopathy; astrocyte
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Bukhari, W.; Barnett, M.H.; Prain, K.; Broadley, S.A. Molecular Pathogenesis of Neuromyelitis Optica. Int. J. Mol. Sci. 2012, 13, 12970-12993.
Bukhari W, Barnett MH, Prain K, Broadley SA. Molecular Pathogenesis of Neuromyelitis Optica. International Journal of Molecular Sciences. 2012; 13(10):12970-12993.
Bukhari, Wajih; Barnett, Michael H; Prain, Kerri; Broadley, Simon A. 2012. "Molecular Pathogenesis of Neuromyelitis Optica." Int. J. Mol. Sci. 13, no. 10: 12970-12993.