2019 Volume 31 Issue 180 Pages J77-J85
In demyelinating diseases such as multiple sclerosis, the regeneration of lost myelin sheaths (remyelination) is clinically important. N-acetyl glucosaminyl transferase IX (GnT-IX, GnT-Vb) is a branching enzyme on O-mannosyl glycan that is expressed exclusively in the brain in vivo. GnT-IX-deficient mice showed enhanced remyelination compared to wild-type mice in a cuprizone-induced demyelination model. In GnT-IX-deficient mice, astrocyte activation was attenuated while oligodendrocyte differentiation was simultaneously promoted, suggesting they are the causes of enhanced remyelination. HNK-1-capped branched O-mannosyl glycan is attached to should-be receptor-type protein tyrosine phosphatase ζ (PTPRZ) and expressed in reactive astrocytes. Moreover, GnT-IX was shown to be involved in PTPRZ lipid raft targeting. GnT-IX-deficient mice showed no obvious abnormalities; therefore, GnT-IX is a potential therapeutic target that promotes remyelination in demyelinating diseases.
