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Review
. 2021 Feb;156(4):403-414.
doi: 10.1111/jnc.15133. Epub 2020 Aug 25.

The role of Sphingolipids in myelination and myelin stability and their involvement in childhood and adult demyelinating disorders

Paola Giussani  1 , Alessandro Prinetti  1 , Cristina Tringali  1
Affiliations
Free article
Review

The role of Sphingolipids in myelination and myelin stability and their involvement in childhood and adult demyelinating disorders

Paola Giussani et al. J Neurochem. 2021 Feb.
Free article

Abstract

Multiple sclerosis (MS) represents the most common demyelinating disease affecting the central nervous system (CNS) in adults as well as in children. Furthermore, in children, in addition to acquired diseases such as MS, genetically inherited diseases significantly contribute to the incidence of demyelinating disorders. Some genetic defects lead to sphingolipid alterations that are able to elicit neurological symptoms. Sphingolipids are essential for brain development, and their aberrant functionality may thus contribute to demyelinating diseases such as MS. In particular, sphingolipidoses caused by deficits of sphingolipid-metabolizing enzymes, are often associated with demyelination. Sphingolipids are not only structural molecules but also bioactive molecules involved in the regulation of cellular events such as development of the nervous system, myelination and maintenance of myelin stability. Changes in the sphingolipid metabolism deeply affect plasma membrane organization. Thus, changes in myelin sphingolipid composition might crucially contribute to the phenotype of diseases characterized by demyelinalization. Here, we review key features of several sphingolipids such as ceramide/dihydroceramide, sphingosine/dihydrosphingosine, glucosylceramide and, galactosylceramide which act in myelin formation during rat brain development and in human brain demyelination during the pathogenesis of MS, suggesting that this knowledge could be useful in identifying targets for possible therapies.

Keywords: demyelination; multiple sclerosis; myelin; sphingolipidoses; sphingolipids.

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References

REFERENCES

    1. Arnon, R., Crisp, E., Kelley, R., Ellison, G. W., Myers, L. W., & Tourtellotte, W. W. (1980). Anti-ganglioside antibodies in multiple sclerosis. Journal of the Neurological Sciences, 46, 179-186.
    1. Askari, V. R., Baradaran Rahimi, V., Tabatabaee, S. A., & Shafiee-Nick, R. (2019). Combination of Imipramine, a sphingomyelinase inhibitor, and β-caryophyllene improve their therapeutic effects on experimental autoimmune encephalomyelitis (EAE). International Immunopharmacology, 77, 105923.
    1. Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). (2009). Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nature Genetics, 41, 824-828.
    1. Baranzini, S. E., Galwey, N. W., Wang, J., Khankhanian, P., Lindberg, R., Pelletier, D., … Barnes, M. R. (2009). Pathway and network-based analysis of genome-wide association studies in multiple sclerosis. Human Molecular Genetics, 18, 2078-2090.
    1. Baranzini, S. E., & Oksenberg, J. R. (2017). The genetics of multiple sclerosis: From 0 to 200 in 50 Years. Trends in Genetics, 33, 960-970.

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