Role of sphingomyelinases in neurological disorders.

Abstract

INTRODUCTION:

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.

AREAS COVERED:

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.

EXPERT OPINION:

More research needs to be carried out to develop pharmacological agents that act on sphingomyelinases, for the prevention or treatment of neurological disorders.

• Authors: Wei-Yi Ong, Deron R Herr, Tahira Farooqui, Eng-Ang Ling, Akhlaq A Farooqui
• Journal: Expert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 19 Issue 12 Pg. 1725-42 ( 2015) ISSN: 1744-7631 [Electronic] England
• PMID: 26243307 (Publication Type: Journal Article, Review)

Chemical References

• Ceramides
• Phosphorylcholine
• Sphingomyelin Phosphodiesterase

Topics

• Animals
• Brain (enzymology, physiopathology)
• Ceramides (metabolism)
• Drug Design
• Humans
• Nervous System Diseases (drug therapy, enzymology, physiopathology)
• Phosphorylcholine (metabolism)
• Sphingomyelin Phosphodiesterase (metabolism)