The presence of glycosylated sterols in EVs (Figure 2C) and CSF indicates that UDP-sugar independent glycolipid synthesis may eliminate the excess lipids from the cell membrane to maintain lipid homeostasis, especially Chol as well as GSL. In Referencesparticular, GBA2 is present on the cytosolic side and may be involved in lipid-induced stress responses in the Golgi or ER lipid bilayer membranes.1) Nagatsuka Y, Horibata Y, Yamazaki Y, Kinoshita M, Shinoda Y, Hashikawa T, Koshino H, Nakamura T, Hirabayashi Y. Phosphatidylglucoside exists as a single molecular species with saturated fatty acyl chains in developing astroglial membranes. Biochemistry (45): 8742-8750, 2006.2) Guy AT, Nagatsuka Y, Ooashi N, Inoue M, Nakata A, Greimel P, Inoue A, Nabetani T, Murayama A, Ohta K, Ito Y, Aoki J, Hirabayashi Y*, Kamiguchi H*. NEURONAL DEVELOPMENT. Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord. Science 349(6251): 974-977, 2015. (*Co-authors)3) Akiyama H, Kobayashi S, Hirabayashi Y, Murakami-Murofushi K. Cholesterol glucosylation is catalyzed by transglucosylation reaction of β-glucosidase 1. Biochem. Biophys. Res. Commun. 441: 838-843, 2013.4) Akiyama H, Nakajima K, Itoh Y, Sayano T, Ohashi Y, Yamaguchi Y, Greimel P, Hirabayashi Y. Aglycon diversity of brain sterylglucosides: structure determination of cholesteryl- and sitosterylglucoside. J. Lipid Res. 57: 2061-2072, 2016.5) Akiyama H, Nagatsuka Y, Sayano T, Nakanishi E, Uemura N, Yuyama K, Yamaguchi Y, Kamiguchi H, Takahashi R, Aerts JMFG, Greimel P, Hirabayashi Y. Glucocerebrosidases catalyze a transgalactosylation reaction that yields a newly identified brain sterol metabolite, galactosylated cholesterol. J Biol Chem. 295(16): 5257-5277, 2020.6) Akiyama H, Ide M, Yamaji T, Mizutani Y, Niimi Y, Mutoh T, Kamiguchi H, Hirabayashi Y. Galabiosylceramide is present in human cerebrospinal fluid. Biochem Biophys Res Commun. 536: 73-79, 2021.7) Hanashima S, Fukuda N, Malabed R, Murata M, Kinoshita M, Greimel P, Hirabayashi Y. β-Glucosylation of cholesterol reduces sterol-sphingomyelin interactions. Biochim Biophys Acta Biomembr. 1;1863(2):183496, 2021. 8) Niimi Y, Mizutani Y, Akiyama H, Watanabe H, Shiroki R, Hirabayashi Y, Hoshinaga K, Mutoh T. Cerebrospinal Fluid Profiles in Parkinson's Disease: No accumulation of glucosylceramide, but significant downregulation of active complement C5 fragment. J Parkinsons Dis. 11:221-232, 2021.9) Akiyama H, Ide M, Yamaji T, Mizutani Y, Niimi Y, Mutoh T, Kamiguchi H, Hirabayashi Y. Galabiosylceramide is present in human cerebrospinal fluid. Biochem Biophys Res Commun. 536:73-79, 2021.83
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