Decreased cholesterol biosynthesis in fibroblasts from patients with Parkinson disease.

Abstract

The underlying cause of cellular degeneration in the substantia nigra of patients with Parkinson disease has not been clearly established. With the objective of investigating whether metabolic abnormalities would be detected in peripheral non-neuronal cells, we began assessing key metabolic parameters in skin fibroblasts of these patients. The present report focuses on the finding of a remarkably reduced cholesterol biosynthetic capability of fibroblasts from patients with Parkinson disease. 14C-Acetate incorporation into cholesterol of these fibroblasts was 27.8 +/- 9.4% that observed in normal fibroblasts, and the reduced cholesterol synthesis was confirmed by measuring the activity of the rate-limiting enzyme HMGCoA reductase which averaged 6.64 +/- 2.50 nmol/h/mg protein in the patient's fibroblasts compared to 14.70 +/- 0.69 nmol/h/mg protein in the control fibroblasts. Cholesterol esterifying activity, as cholesteryl oleate formed from 14C-oleate, of the fibroblasts from Parkinson patients, was reduced by an average 43%. Two hypotheses are put forward to link these findings with the current experimental evidences for both increased lipid peroxidation and defective mitochondrial respiratory chain complex I activity in a number of cell types from Parkinson patients. Considering that decreased cholesterol biosynthesis has been detected in all the Parkinson cell lines thus far investigated, it is suggested that this may be a hallmark of the disease.