Abstract
Ceramide, the precursor of all complex sphingolipids, is a potent signaling molecule that mediates key events of cellular pathophysiology. In the nervous system, the sphingolipid metabolism has an important impact. Neurons are polarized cells and their normal functions, such as neuronal connectivity and synaptic transmission, rely on selective trafficking of molecules across plasma membrane. Sphingolipids are abundant on neural cellular membranes and represent potent regulators of brain homeostasis. Ceramide intracellular levels are fine-tuned and alteration of the sphingolipid–ceramide profile contributes to the development of age-related, neurological and neuroinflammatory diseases. The purpose of this review is to guide the reader towards a better understanding of the sphingolipid–ceramide pathway system. First, ceramide biology is presented including structure, physical properties and metabolism. Second, we describe the function of ceramide as a lipid second messenger in cell physiology. Finally, we highlight the relevance of sphingolipids and ceramide in the progression of different neurodegenerative diseases.
Highlights
Ceramides are a family of lipid molecules that consist of sphingoid long-chain base linked to an acyl chain via an amide bond
Sphingoid bases are of three general chemical types: sphingosine, dihydrosphingosine and phytosphingosine
Based on the nature of the sphingoid base backbone, we can distinguish three main subgroups in the ceramide family: the compound named ceramide contains sphingosine, which has a trans-double bond at the C4–5 position in the sphingoid base backbone; dihydroceramide, the inactive precursor of ceramide, contains sphinganine, which presents a saturated sphingoid backbone devoid of the 4,5-trans-double bond; phytoceramide, the yeast counterpart of the mammalian ceramide, contains phytosphingosine, which has a hydroxyl group at the C4 position [1] (Fig. 1)
Summary
Ceramides are a family of lipid molecules that consist of sphingoid long-chain base linked to an acyl chain via an amide bond. Ceramides differ from each other by length, hydroxylation, and saturation of both the sphingoid base and fatty acid moieties. Based on the nature of the sphingoid base backbone, we can distinguish three main subgroups in the ceramide family: the compound named ceramide contains sphingosine, which has a trans-double bond at the C4–5 position in the sphingoid base backbone; dihydroceramide, the inactive precursor of ceramide, contains sphinganine, which presents a saturated sphingoid backbone devoid of the 4,5-trans-double bond; phytoceramide, the yeast counterpart of the mammalian ceramide, contains phytosphingosine, which has a hydroxyl group at the C4 position [1] (Fig. 1). The fatty acid components of ceramides vary widely in composition, but they are typically long. Their acyl chain lengths range from 14 to 26 carbon atoms (or greater), the most common fatty acids are palmitic (C16:0) and stearic (C18:0) non-hydroxy fatty acids. The fatty acids are commonly saturated or mono-unsaturated. a-Hydroxylated fatty acids (a hydroxyl group at the C-2 position) and x-hydroxy fatty acid (a hydroxyl group on the terminal C atom) are often present as well [2]
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