Abstract
Lysosomal storage diseases (LSDs) are mainly caused by the defective activity of lysosomal hydrolases. A sub-class of LSDs are the sphingolipidoses, in which sphingolipids accumulate intra-cellularly. We here discuss the role of innate immunity in the sphingolipidoses, and compare the pathways of activation in two classical sphingolipidoses, namely Gaucher disease and Sandhoff disease, and in Niemann-Pick C disease, in which the main storage material is cholesterol but sphingolipids also accumulate. We discuss the mechanisms leading to neuroinflammation, and the different pathways of neuroinflammation in the different diseases, and suggest that intervention in these pathways may be a useful therapeutic approach to address these devastating human diseases.
Acknowledgments
We thank Iris Zelnik for help with the figure and Dr. Tamar Farfel-Becker for her helpful comments.
References
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©2015 by De Gruyter
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: Molecular Medicine of Sphingolipids
- HIGHLIGHT: MOLECULAR MEDICINE OF SPHINGOLIPIDS
- The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
- Sphingolipids in viral infection
- Tackling the biophysical properties of sphingolipids to decipher their biological roles
- Ceramide and sphingosine in pulmonary infections
- Molecular mechanisms of erythrocyte aging
- Sphingolipids in liver injury, repair and regeneration
- Ultrasound-stimulated microbubble enhancement of radiation response
- Innate immune responses in the brain of sphingolipid lysosomal storage diseases
- Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways
- The role of sphingolipids in endothelial barrier function
- The effect of altered sphingolipid acyl chain length on various disease models
- Secretory sphingomyelinase in health and disease
- Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic
- Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation
- The molecular medicine of acid ceramidase
- Caenorhabditis elegans as a model to study sphingolipid signaling
- S1PR4 is required for plasmacytoid dendritic cell differentiation
- Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors
- Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
- Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
- Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
- Obituary
- The life and work of Dr. Robert Bittman (1942–2014)
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: Molecular Medicine of Sphingolipids
- HIGHLIGHT: MOLECULAR MEDICINE OF SPHINGOLIPIDS
- The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
- Sphingolipids in viral infection
- Tackling the biophysical properties of sphingolipids to decipher their biological roles
- Ceramide and sphingosine in pulmonary infections
- Molecular mechanisms of erythrocyte aging
- Sphingolipids in liver injury, repair and regeneration
- Ultrasound-stimulated microbubble enhancement of radiation response
- Innate immune responses in the brain of sphingolipid lysosomal storage diseases
- Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways
- The role of sphingolipids in endothelial barrier function
- The effect of altered sphingolipid acyl chain length on various disease models
- Secretory sphingomyelinase in health and disease
- Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic
- Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation
- The molecular medicine of acid ceramidase
- Caenorhabditis elegans as a model to study sphingolipid signaling
- S1PR4 is required for plasmacytoid dendritic cell differentiation
- Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors
- Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
- Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
- Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
- Obituary
- The life and work of Dr. Robert Bittman (1942–2014)