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The Glycosphingolipid Hydrolases in the Central Nervous System

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Abstract

Glycosphingolipids are a large group of complex lipids particularly abundant in the outer layer of the neuronal plasma membranes. Qualitative and quantitative changes in glycosphingolipids have been reported along neuronal differentiation and aging. Their half-life is short in the nervous system and their membrane composition and content are the result of a complex network of metabolic pathways involving both the de novo synthesis in the Golgi apparatus and the lysosomal catabolism. In particular, most of the enzymes of glycosphingolipid biosynthesis and catabolism have been found also at the plasma membrane level. Their action could be responsible for the fine tuning of the plasma membrane glycosphingolipid composition allowing the formation of highly specialized membrane areas, such as the synapses and the axonal growth cones. While the correlation between the changes of GSL pattern and the modulation of the expression/activity of different glycosyltransferases during the neuronal differentiation has been widely discussed, the role of the glycohydrolytic enzymes in this process is still little explored. For this reason, in the present review, we focus on the main glycolipid catabolic enzymes β-hexosaminidases, sialidases, β-galactosidases, and β-glucocerebrosidases in the process of the neuronal differentiation.

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Abbreviations

PM:

Plasma membrane

GSL:

Glycosphingolipid

GalNAc:

N-acetyl-galactosaminide

Hex:

β-hexosaminidase

GnRH:

Gonadotropin-releasing hormone

RA:

Retinoic acid

MUG:

4-Methylumbelliferyl-N-acetyl-β-d-glucosaminide

MUGS:

4-Methylumbelliferyl-N-acetyl-β-d-glucosaminide-6-sulfate

MUB-Gal:

4-Methylumbelliferyl-β-d-galactopyranoside

NSCs:

Neuronal stem cells

GlcSph:

Glucosyl sphingosine

GlcCer:

Glucosyl ceramide

CBE:

Conduritol B epoxide

GD:

Gaucher disease

PD:

Parkinson disease

AMP-DNM:

N-(5-Adamantane-1-yl-methoxy)pentyl-deoxynojirimycin

KO:

Knockout

WT:

Wild type

CNS:

Central nervous system

SL:

Sphingolipid

Cer:

Ceramide

FBS:

Fetal bovine serum

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Authors and Affiliations

  1. Department of Medical Biotechnology and Translational Medicine, University of Milano, Via Fratelli Cervi 93, 20090, Segrate, Italy

    Massimo Aureli, Maura Samarani, Nicoletta Loberto, Rosaria Bassi, Valentina Murdica, Simona Prioni, Alessandro Prinetti & Sandro Sonnino

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  1. Massimo Aureli
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  2. Maura Samarani
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  3. Nicoletta Loberto
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  4. Rosaria Bassi
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  5. Valentina Murdica
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  6. Simona Prioni
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  7. Alessandro Prinetti
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  8. Sandro Sonnino
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Correspondence to Sandro Sonnino.

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Aureli, M., Samarani, M., Loberto, N. et al. The Glycosphingolipid Hydrolases in the Central Nervous System. Mol Neurobiol 50, 76–87 (2014). https://doi.org/10.1007/s12035-013-8592-6

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  • DOI: https://doi.org/10.1007/s12035-013-8592-6

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