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.

Keywords: Alzheimer’s disease; PLA2; antidepressant; apoptosis; ceramide; cholesterol; cortex; glia; neurodegeneration; sphingolipids; sphingomyelinase; striatum.