Disease modifying therapy for Parkinson's disease focusing on lipid metabolic enzymes

Abstract

Parkinson's disease is regarded as the second most prevalent neurodegenerative disorder after Alzheimer's disease. The characteristic pathological finding in cases of Parkinson's disease is dopaminergic neuronal degeneration with Lewy body. Braak et al hypothesized that Parkinson's disease might be distributed from peripheral autonomic neurons to the central nervous system. The progression of Parkinson's disease might be caused by prion–like dissemination of alpha–synuclein, which is known as the main component of Lewy body. Thus, it might be expected that prevention of alpha–synuclein aggregation is possible through disease–modifying therapy. Alpha–synuclein is associated with lipids and the perturbation of the association is caused by the aggregation of alpha–synuclein. Furthermore, genetic dysfunction of phospholipid and glucolipid enzymes, such as GBA mutation and PLA2G6 mutations, is associated with Parkinson's disease with Lewy body. Therefore, elucidation of the pathomechanisms in Parkinson's disease related to the perturbation of lipid metabolism might shed light on the development of disease–modifying therapy.