Elevated activity of phospholipid biosynthetic enzymes in substantia nigraof patients with Parkinson's disease

We reported that the activities of phospholipase A(2), phosphocholine cytid ylyltransferase and phosphoethanolamine cytidylyltransferase. key phospholi pid metabolic enzymes, are low in substantia nigra of normal human brain an d that this might reduce the ability of nigral neurons to repair damage to cell membranes. To determine whether adaptive changes in nigral phospholipi d metabolism can occur in idiopathic Parkinson's disease we compared activi ties of 11 catabolic and anabolic enzymes in autopsied brain of 10 patients with Parkinson's disease to those in control subjects Nigral activity of t he catabolic enzyme phospholipase A(2) was normal in the Parkinson's diseas e group, whereas that of the biosynthetic enzymes phosphoethanolamine cytid ylyltransferase. phosphocholine cytidylyltransferase and phosphatidylserine synthase were elevated 193. 48 and 38%, respectively, possibly representin g a compensatory response to repair membrane phospholipids. Enzyme activiti es were normal in all other brain areas with the exception of increased (+2 6%) activity of calcium-stimulated phospholipase A(2) in putamen, a change which could be consequent to either decreased dopaminergic striatal input o r to a dopamine nerve terminal degenerative process. Our data indicate that the normally low rate of membrane phospholipid synth esis in the substantia nigra, the primary area of neurodegeneration in Park insons disease, is increased during the course of the disorder. We suggest that pharmacotherapies which augment this compensatory response might have utility as a treatment for Parkinson's disease. (C) 2001 Published by Elsev ier Science Ltd on behalf of IBRO.