Contribution of cholesterol and oxysterols to the pathophysiology of Parkinson's disease

Neurodegenerative diseases are a major public health issue worldwide. Some countries, including France, have engaged in research into the causes of Parkinson's disease, Alzheimer's disease, and multiple sclerosis and the management of these patients. It should lead to a better understanding of the mechanisms leading to these diseases including the possible involvement of lipids in their pathogenesis. Parkinson's disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of a-synuclein (Lewy bodies). Several in vivo studies have shown a relationship between the lipid profile [cholesterol, oxidized cholesterol products (oxysterols) formed either enzymatically or by auto-oxidation], the use of drugs regulating cholesterol levels, and the development of Parkinson's disease. Several oxysterols are present in the brain and could play a role in the development of this disease, particularly in the accumulation of a-synuclein, and through various side effects, such as oxidation, inflammation, and cell death. Consequently, in Parkinson's disease, some oxysterols could contribute to the pathophysiology of the disease and constitute potential biomarkers or therapeutic targets.