Glycolipids: Essential regulator of neuro-inflammation, metabolism and gliomagenesis

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 10; pp. 2479 - 2484
• Main Authors: Furukawa, Koichi, Ohmi, Yuhsuke, Ji, Shuting, Zhang, Pu, Bhuiyan, Robiul H., Ohkawa, Yuki, Tajima, Orie, Hashimoto, Noboru, Furukawa, Keiko
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2017
• Subjects: adipocytes; Animals; Astrocyte; Complement; Complement System Proteins - genetics; Complement System Proteins - metabolism; energy; Ganglioside; gangliosides; Gangliosides - metabolism; Gene Expression Regulation, Neoplastic; gene targeting; genetic background; genetically modified organisms; Glioma; Glioma - genetics; Glioma - metabolism; Glioma - pathology; glycosyltransferases; Humans; hypothalamus; Inflammation; Knockout; knockout mutants; leptin; Leptin - genetics; Leptin - metabolism; leptin receptors; Membrane Microdomains - chemistry; Membrane Microdomains - metabolism; Membrane Microdomains - pathology; metabolism; Mice; Mice, Knockout; N-Acetylgalactosaminyltransferases - deficiency; N-Acetylgalactosaminyltransferases - genetics; Neoplasms, Nerve Tissue - genetics; Neoplasms, Nerve Tissue - metabolism; Neoplasms, Nerve Tissue - pathology; Nerve Tissue - metabolism; Nerve Tissue - pathology; Neurodegeneration; neurodegenerative diseases; neurons; Neurons - metabolism; Neurons - pathology; patients; phenotype; Receptors, Leptin - genetics; Receptors, Leptin - metabolism; secretion; Sialyltransferases - deficiency; Sialyltransferases - genetics; Ganglioside; Glioma; Neurodegeneration; Inflammation; Complement; Astrocyte; Knockout
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2017.06.007

Gene knockout mice of glycosyltransferases have clearly showed roles of their products in the bodies, while there are examples where phenotype of knockout was much less severe than expected probably due to functional redundancy. The most striking novel finding obtained from ganglioside-deficient mice was that progressive inflammatory reaction took place, leading to neurodegeneration. In particular, dysfunction of complement-regulatory proteins due to deteriorated architecture of lipid rafts seemed to be essential mechanisms for the inflammation. Furthermore, roles of gangliosides in neurons were demonstrated by neuron-specific transgenic of B4galnt1 with genetic background of B4galnt1 deficiency. From study of gene knockout mice of St8sia1, new roles of b-series gangliosides in leptin secretion from adipocytes, and roles of a-series gangliosides in leptin receptor, ObR in hypothalamus were demonstrated, leading to apparent intact balance of energy. Essential roles of b-series gangliosides in malignant properties of gliomas were also shown, suggesting their roles in the regulation of inflammation and proliferation in nervous tissues. How to apply these findings for the control of newly discovered patients with ganglioside deficiency remains to be investigated. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa. •Knockout of ganglioside synthase revealed a variety of neurological disorders.•Glycolipids play important roles in nervous, immune and endocrine systems.•How to apply new findings for diseases with abnormal glycosylation is next issue.