ROLE OF SPHK2/S1P SIGNALLING IN REGULATING MITOCHONDRIAL FUNCTION IN THE MPTP – INDUCED MOUSE MODEL OF PARKINSON’S DISEASE AND IN THE MPP+-TREATED MN9D CELLS.

Abstract

Sphingosine kinases (Sphk1 and Sphk2) are the major rate limiting enzymes in the sphingolpid metabolic pathway which produces the enigmatic S1P that controls diverse physiological processes in the brain. The role of the second isofom Sphk2 in neurodegenerative disorder like PD remains elusive. Gene expression study and protein analysis revealed that the expression pattern of Sphk2 decreased significantly in the substantia nigra region of the MPTP-induced mouse model of Parkinson?s disease. Localization studies showed that Sphk2 was predominantly present in the mitochondria proposing for its potential role in the mitochondria. Since mitochondrial dysfunction has been reported to be the major pathological event in Parkinson?s disease, the present study focused on the role of Sphk2 /S1P signalling in regulating mitochondrial functions in the MPTP induced mouse model of Parkinson?s disease and in the MPP+ treated MN9D cells.