Sphingomyelinases as modulators of synaptic transmission

Abstract

The brain has a high content of sphingomyelin, which is involved in the formation of plasma membranes and myelin, and is also an important for the organization of membrane microdomains (lipid rafts). Lipid rafts, as well as derivatives of sphingomyelin hydrolysis (ceramide, sphingosine, sphingosine-1-phosphate), are vital for synaptic transmission and its regulation. One of the main pathways to control the level of sphingomyelin and its derivatives is cleavage of membrane sphingomyelin by sphingomyelinases. Sphingomyelinases are localized inside the cell (in association with the plasma membrane, in lysosomes, endosomes, Golgi complex and endoplasmic reticulum) as well as can be secreted into the extracellular space. The levels and activity of sphingomyelinases significantly increase under the action of various stressful stimuli (including inflammation). At the same time, sphingomyelinase activity deficiency causes diseases with severe neurological manifestations. In the present review, we summarized the data on the currently known effects of acidic and neutral sphingomyelinases on pre- and postsynaptic processes, as well as about the synaptic localization of sphingomyelinases. In addition, a brief analysis of possible synaptic dysfunction due to hypo- or hyperfunction of sphingomyelinases in a number of neurological diseases is given. Thus, sphingomyelinases are considered as important modulators of synaptic transmission at the pre- and postsynaptic levels in normal and pathological conditions.