Next Article in Journal
Bifidobacterium and Lactobacillus Composition at Species Level and Gut Microbiota Diversity in Infants before 6 Weeks
Next Article in Special Issue
Light Stress-Induced Increase of Sphingosine 1-Phosphate in Photoreceptors and Its Relevance to Retinal Degeneration
Previous Article in Journal
Functional Analysis of M-Locus Protein Kinase Revealed a Novel Regulatory Mechanism of Self-Incompatibility in Brassica napus L.
Previous Article in Special Issue
Cardiodynamic Interactions between Two S1P1 Receptor Modulators in an Experimental Clinical Setting: Different Pharmacokinetic Properties as an Opportunity to Mitigate First-Dose Heart Rate Effects
Open AccessReview

The Link between Gaucher Disease and Parkinson’s Disease Sheds Light on Old and Novel Disorders of Sphingolipid Metabolism

1
Department of Health Science, University of Milan, 20142 Milano, Italy
2
Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(13), 3304; https://doi.org/10.3390/ijms20133304
Received: 6 June 2019 / Revised: 26 June 2019 / Accepted: 29 June 2019 / Published: 5 July 2019
(This article belongs to the Special Issue Sphingolipids: Metabolic Functions and Disorders)
Sphingolipid metabolism starts with the biosynthesis of ceramide, a bioactive lipid and the backbone for the biosynthesis of complex sphingolipids such as sphingomyelin and glycosphingolipids. These are degraded back to ceramide and then to sphingosine, which enters the ceramide–sphingosine-1-phosphate signaling pathway or is further degraded. Several enzymes with multiple catalytic properties and subcellular localizations are thus involved in such metabolism. Hereditary defects of lysosomal hydrolases have been known for several years to be the cause of lysosomal storage diseases such as gangliosidoses, Gaucher disease, Niemann–Pick disease, Krabbe disease, Fabry disease, and Farber disease. More recently, many other inborn errors of sphingolipid metabolism have been recognized, involving enzymes responsible for the biosynthesis of ceramide, sphingomyelin, and glycosphingolipids. Concurrently, epidemiologic and biochemical evidence has established a link between Gaucher disease and Parkinson’s disease, showing that glucocerebrosidase variants predispose individuals to α-synuclein accumulation and neurodegeneration even in the heterozygous status. This appears to be due not only to lysosomal overload of non-degraded glucosylceramide, but to the derangement of vesicle traffic and autophagy, including mitochondrial autophagy, triggered by both sphingolipid intermediates and misfolded proteins. In this review, old and novel disorders of sphingolipid metabolism, in particular those of ganglioside biosynthesis, are evaluated in light of recent investigations of the link between Gaucher disease and Parkinson’s disease, with the aim of better understanding their pathogenic mechanisms and addressing new potential therapeutic strategies. View Full-Text
Keywords: autophagy; ganglioside; lysosome; rare disease autophagy; ganglioside; lysosome; rare disease
Show Figures

Figure 1

MDPI and ACS Style

Indellicato, R.; Trinchera, M. The Link between Gaucher Disease and Parkinson’s Disease Sheds Light on Old and Novel Disorders of Sphingolipid Metabolism. Int. J. Mol. Sci. 2019, 20, 3304.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop