title: Role of sphingomyelinases in neurological disorders.
abstract: BACKGROUND
  Sphingomyelinases, which catalyze the hydrolysis of sphingomyelin to ceramide and phosphorylcholine, are abundant in the brain. These enzymes are a major, rapid source of ceramide production not only during physiological responses to receptor stimulation, but also in neurological disorders.
  
  
  METHODS
  We covered an introduction to sphingomyelinases and its enzymatic product ceramide, in membrane domains or lipid rafts and the nucleus; followed by crosstalk between sphingomyelinase and cytosolic phospholipase A2 (cPLA2) catalysed products including arachidonic acid, functions of acid sphingomyelinase (aSMase) and neutral sphingomyelinase (N-SMase) in neurons, neuronal progenitor cells, glial cells, and brain endothelial cells; alterations in acid and N-SMases in Niemann Pick Disease Type A, major depression, Alzheimer's disease, cerebral ischemia, and pain; and recent developments in identification of inhibitors to sphingomyelinases. As literature search methodology, we did key word searches using Pubmed.
  
  
  CONCLUSIONS
  More research needs to be carried out to develop pharmacological agents that act on sphingomyelinases, for the prevention or treatment of neurological disorders.
authors.affiliation: a 1 National University of Singapore, Department of Anatomy , Singapore 119260, Singapore +65 6516 3662 ; +65 6778 7643 ; wei_yi_ong@nuhs.edu.sg.|b 2 National University of Singapore, Neurobiology and Ageing Research Programme , Singapore 119260, Singapore.
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Ong
authors.affiliation: c 3 National University of Singapore, Department of Pharmacology , Singapore 119260, Singapore.
authors.forename: Deron R
authors.initials: DR
authors.lastname: Herr
authors.affiliation: d 4 The Ohio State University, Department of Molecular and Cellular Biochemistry , Columbus, OH, USA.
authors.forename: Tahira
authors.initials: T
authors.lastname: Farooqui
authors.affiliation: a 1 National University of Singapore, Department of Anatomy , Singapore 119260, Singapore +65 6516 3662 ; +65 6778 7643 ; wei_yi_ong@nuhs.edu.sg.
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.affiliation: d 4 The Ohio State University, Department of Molecular and Cellular Biochemistry , Columbus, OH, USA.
authors.forename: Akhlaq A
authors.initials: AA
authors.lastname: Farooqui
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000503:physiopathology; D002518:Ceramides / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D010767:Phosphorylcholine / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*
chemical_list: D002518:Ceramides; D010767:Phosphorylcholine; D013108:Sphingomyelin Phosphodiesterase
keywords: Alzheimer’s disease; PLA2; antidepressant; apoptosis; ceramide; cholesterol; cortex; glia; neurodegeneration; sphingolipids; sphingomyelinase; striatum