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Review
. 2021 Jun 25;11(7):945.
doi: 10.3390/biom11070945.

Ceramide Metabolism and Parkinson's Disease-Therapeutic Targets

Antía Custodia  1 , Marta Aramburu-Núñez  1 , Clara Correa-Paz  1 , Adrián Posado-Fernández  1 , Ana Gómez-Larrauri  2   3 , José Castillo  1 , Antonio Gómez-Muñoz  2 , Tomás Sobrino  1 , Alberto Ouro  1
Affiliations
Review

Ceramide Metabolism and Parkinson's Disease-Therapeutic Targets

Antía Custodia et al. Biomolecules. .

Abstract

Ceramide is a bioactive sphingolipid involved in numerous cellular processes. In addition to being the precursor of complex sphingolipids, ceramides can act as second messengers, especially when they are generated at the plasma membrane of cells. Its metabolic dysfunction may lead to or be a consequence of an underlying disease. Recent reports on transcriptomics and electrospray ionization mass spectrometry analysis have demonstrated the variation of specific levels of sphingolipids and enzymes involved in their metabolism in different neurodegenerative diseases. In the present review, we highlight the most relevant discoveries related to ceramide and neurodegeneration, with a special focus on Parkinson's disease.

Keywords: Parkinson’s disease; ceramide; ceramide synthase; neurodegeneration; sphingolipidomics; sphingolipids; sphingomyelinase; β-GCase.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Sphingolipid metabolism. Solid arrows represent single reactions, whereas dashed arrows represent various step reactions. Interrogation marks with dashed arrows indicate unidentified mechanisms. Sphingomyelinase (SMase), sphingomyelin synthase (SMS), acid-sphingomyelinase (aSMase), Ceramide 1-phosphate phosphatase (C1PP), ceramide kinase (CERK), Serine palmitoyl transferase (SPT), 3-ketosphinganine reductase (KDR), Ceramide Synthase (CerS), sphingosine kinase (SphK), sphingosine 1-phosphate phosphatase (SPP), Sphingosine 1-phosphate lyase (S1P lyase) are represented by their acronyms.
Figure 2
Figure 2
Schematic representation of the influence of genetic mutations involved in PD with Cer metabolism. Genes are represented in italics and red color. Red lines circled at the end indicate increased activity, while a traversed lines at the end indicate inhibition or dysfunction. Neutral Sphingomyelinase 2 (nSMase2), acid sphingomyelinase (aSMase), Ceramide Synthase (CerS), acid β-glucosidase (β-GCase), Ceramide (Cer), GlucosylCeramide (GlcCer) and reactive oxygen species (ROS) are represented by their acronyms.
See this image and copyright information in PMC

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