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Review
. 2020 Jun 2;9(6):1379.
doi: 10.3390/cells9061379.

Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration

Carolina Duarte  1 , Juliet Akkaoui  1 , Chiaki Yamada  1 , Anny Ho  1 , Cungui Mao  2   3 , Alexandru Movila  1   4
Affiliations
Review

Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration

Carolina Duarte et al. Cells. .

Abstract

Ceramide and sphingosine are important interconvertible sphingolipid metabolites which govern various signaling pathways related to different aspects of cell survival and senescence. The conversion of ceramide into sphingosine is mediated by ceramidases. Altogether, five human ceramidases-named acid ceramidase, neutral ceramidase, alkaline ceramidase 1, alkaline ceramidase 2, and alkaline ceramidase 3-have been identified as having maximal activities in acidic, neutral, and alkaline environments, respectively. All five ceramidases have received increased attention for their implications in various diseases, including cancer, Alzheimer's disease, and Farber disease. Furthermore, the potential anti-inflammatory and anti-apoptotic effects of ceramidases in host cells exposed to pathogenic bacteria and viruses have also been demonstrated. While ceramidases have been a subject of study in recent decades, our knowledge of their pathophysiology remains limited. Thus, this review provides a critical evaluation and interpretive analysis of existing literature on the role of acid, neutral, and alkaline ceramidases in relation to human health and various diseases, including cancer, neurodegenerative diseases, and infectious diseases. In addition, the essential impact of ceramidases on tissue regeneration, as well as their usefulness in enzyme replacement therapy, is also discussed.

Keywords: ceramidases; ceramides; infectious diseases; inflammation; neurodegenerative diseases.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Role of ceramidases in ceramide metabolism. Ceramide in mammalian cells may be generated: (1) via the de novo synthesis pathway, which begins with the condensation of L-serine and Palmitoyl-CoA); (2) by the hydrolysis of sphingomyelin and glucosylceramide; or (3) from the dephosphorylation of ceramide-1-phosphate. Ceramidase is an enzyme that cleaves fatty acids from ceramide, producing sphingosine. Sphingosine may then be phosphorylated by a sphingosine kinase to form sphingosine-1-phosphate. SMase—sphingomyelinase; GCS—glucosylceramide synthase.
Figure 2
Figure 2
Pathological consequences of ceramidase dysregulation in mammalian cells which occur upon a loss or a gain of function.
Figure 3
Figure 3
Overexpression of acid (ACDase), neutral (NCDase), and alkaline (ALKCDase) ceramidases in specific types of cancer.
Figure 4
Figure 4
Potential therapeutic targeting of acid (ACDase), neutral (NCDase), and alkaline (ALKCDase) ceramidases. *Unspecified class of ALKCDase [80].
See this image and copyright information in PMC

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