title: Acid ceramidase and the treatment of ceramide diseases: The expanding role of enzyme replacement therapy.
abstract: Ceramides are a diverse group of sphingolipids that play important roles in many biological processes. Acid ceramidase (AC) is one key enzyme that regulates ceramide metabolism. Early research on AC focused on the fact that it is the enzyme deficient in the rare genetic disorder, Farber Lipogranulomatosis. Recent research has revealed that deficiency of the same enzyme is responsible for a rare form of spinal muscular atrophy associated with myoclonic epilepsy (SMA-PME). Due to their diverse role in biology, accumulation of ceramides also has been implicated in the pathobiology of many other common diseases, including infectious lung diseases, diabetes, cancers and others. This has revealed the potential of AC as a therapy for many of these diseases. This review will focus on the biology of AC and the potential role of this enzyme in the treatment of human disease.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: edward.schuchman@mssm.edu.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Schuchman
mesh_terms: D055573:Acid Ceramidase / Q000235:genetics / Q000627:therapeutic use*; D000818:Animals; D001168:Arthritis / Q000188:drug therapy / Q000378:metabolism; D001424:Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D056947:Enzyme Replacement Therapy; D004831:Epilepsies, Myoclonic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D055577:Farber Lipogranulomatosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009134:Muscular Atrophy, Spinal / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D012162:Retinal Degeneration / Q000188:drug therapy / Q000378:metabolism; D013106:Sphingolipidoses / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
chemical_list: D002518:Ceramides; C526693:ASAH1 protein, human; D055573:Acid Ceramidase; C526734:Asah1 protein, mouse
keywords: Cell signaling; Ceramide; Enzymes; Lysosomal storage diseases; Sphingolipids