Inflammatory response and its relation to sphingolipid metabolism proteins: Chaperones as potential indirect anti-inflammatory agents

Lysosome is the organelle responsible for breaking down macromolecules to maintain homeostasis and to fight infection. The disruption of normal lysosomal function due to mutations in the sphingolipid metabolism proteins leads to a class of lysosomal storage diseases (LSDs). Defective autophagy and activation of inflammation are observed in most LSDs. The crosstalk between these key metabolic pathways suggests that therapeutic approaches used in the treatment of LSDs may provide anti-inflammatory therapies against chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease. Here, we review the role of sphingolipids in the inflammatory response and build a protein-protein interaction network for proteins related with sphingolipid metabolism and inflammation to identify key interaction partners for the crosstalk between sphingolipids and inflammation. In addition, we present an overview of LSDs in relation with sphingolipids and inflammation, and review the pharmacological chaperones identified for these diseases.