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The Role of the Ceramide Acyl Chain Length in Neurodegeneration: Involvement of Ceramide Synthases

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Abstract

Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable attention in the past few years due to the discovery that ceramide plays vital roles as an intracellular messenger. Ceramide, which consists of a sphingoid long chain base to which a fatty acid is N-acylated, is synthesized in mammals by a family of ceramide synthases (CerS), each of which uses a restricted subset of fatty acyl CoAs for N-acylation. Sphingolipids are found at high levels in nervous tissue, where they perform a variety of important functions in both the adult and the maturing brain. We now review what is known about the role of the acyl chain composition of ceramides and sphingolipids in normal brain development and in neurological diseases. Specifically, we attempt to integrate the information that is available about CerS expression and activity in the brain with the changes in the acyl chain composition of ceramide and complex sphingolipids in a number of neurodegenerative diseases and conditions, such as metachromatic leukodystrophy, neuronal ceroid lipofuscinoses, HIV infection, aging, Alzheimer’s disease, ischemia, and epilepsy. We conclude that understanding the direct relationship between the CerS proteins and neurological conditions will be of great importance for delineating the precise roles of sphingolipids in the brain and is likely to be the subject of intense research activity in the years ahead.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

ApoE:

Apolipoprotein E

ASA:

Arylsulfatase A

CerS:

Ceramide synthase

CGT:

Ceramide galactosyltransferase

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CST:

Cerebroside sulfotransferase

GalCer:

Galactosylceramide

GDF1:

Growth/differentiation factor 1

GlcCer:

Glucosylceramide

GSLs:

Glycosphingolipids

HexCer:

Hexosylceramide

HIVD:

HIV dementia

Hox:

Homeobox

MLD:

Metachromatic leukodystrophy

NCL:

Neuronal ceroid lipofuscinoses

PS1:

Presenilin 1

SLs:

Sphingolipids

SGalCer:

Sulfogalactosylceramide

SM:

Sphingomyelin

TLC:

Tram-lag-CLN8

uog1:

Upstream of GDF1

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Acknowledgments

Work in the Futerman laboratory on the CerS proteins is supported by the Israel Science Foundation (1404/07), the National Institutes of Health (GM076217), the Minerva Foundation, and the U.S.-Israel Binational Science Foundation. A.H. Futerman is the The Joseph Meyerhoff Professor of Biochemistry at the Weizmann Institute of Science and the head of the Nella and Leon Benoziyo Center for Neurological Diseases.

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Ben-David, O., Futerman, A.H. The Role of the Ceramide Acyl Chain Length in Neurodegeneration: Involvement of Ceramide Synthases. Neuromol Med 12, 341–350 (2010). https://doi.org/10.1007/s12017-010-8114-x

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  • DOI: https://doi.org/10.1007/s12017-010-8114-x

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