Decreased Cholesterol Biosynthesis in Fibroblasts from Patients with Parkinson Disease |
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| Institution: | 1. Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China;2. Department of Neurology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China;3. Beijing Institute for Brain Disorders Parkinson''s Disease Center, Beijing, China;4. Department of Neurology, The Affiliated Sanming First Hospital of Fujian Medical University, Sanming, Fujian, China;5. Department of Neurology, West China Hospital of Sichuan University, Chengdu, China;6. National Human Genome Center in Beijing, Beijing, China;7. Department of Neurology, Xiangya Hospital of Central South University, Changsha, China;8. Key Laboratory on Neurodegenerative Disease of Ministry of Education, Beijing, China;9. Key Laboratory on Parkinson''s Disease of Beijing, Beijing, China;1. Department of Grain Science and Industry, Kansas State University, Manhattan, KS 66506, USA;2. USDA-ARS, Center for Grain and Animal Health Research, Manhattan, KS 66502, USA;1. Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul 120-749, Republic of Korea;2. Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-749, Republic of Korea;1. Dipartimento Energia, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy;2. Department of Medical Sciences, University of Torino, Corso A.M. Dogliotti 14, 10126 Torino, Italy;1. Department of Neurosurgery, K.E.M. Hospital and Seth G.S. Medical College, Parel, Mumbai, India;2. Consultant Neurosurgeon, Lilavati Hospital and Research Centre, Bandra (E), Mumbai, India;2. Department of Pathology, HUSLAB, Helsinki University Central Hospital, Helsinki, Finland;3. Clinical Laboratory, Lab21 Ltd, Cambridge, United Kingdom;4. Division of Pulmonary Medicine, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland |
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| 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 per-oxidation 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. |
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