Could Galectin-3 be a key player in the etiology of neuromyelitis optica spectrum disorder?

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a chronic, inflammatory, demyelinating disorder of the central nervous system (CNS) characterized primarily by transverse myelitis (TM) and optic neuritis (ON). Serum antibodies of the IgG class to the water channel protein aquaporin-4 (AQP4) are associated with NMOSD in most cases. These antibodies are thought to cause functional abnormality or changed expressional pattern of AQP4 channel proteins in the CNS lesions. Activation of microglia is one of the chief antibody-mediated effects in NMOSD and it has opposing detrimental and protective effects in NMOSD. On the one hand, it promotes neuroinflammation, demyelination and BBB breakdown. On the other, it aids in remyelination. What controls the switch between these effects is unknown. Recently, Galectin- 3, a lectin, has been identified as a key player in several neurodegenerative diseases. In transient focal brain ischemia, alzheimer's disease (AD), huntington disease (HD), and experimental autoimmune encephalitis (EAE), Galectin-3 promotes microglia-mediated inflammation. Conversely, in amyotrophic lateral sclerosis (ALS), Galectin-3 reduces inflammation. It also suppresses Th17 cytokines, which play a crucial role in NMOSD pathogenesis. Being devoid of a leader signal, Gal-3 localizes in different cellular compartments and is subject to various post-translational modifications. These reasons explain why Galectin-3 expression has opposing effects under different physiological conditions. Microglia-mediated inflammation in NMOSD has not been extensively studied. The factors that regulate microglia-mediated inflammation in NMOSD are unknown. Here, I hypothesize that Galectin-3 might be an etiological factor in NMOSD that regulates microglia-mediated inflammation. Analysing the role of Gal-3 in NMOSD could help in the development of novel therapies to treat NMOSD.