Membrane lipids as therapeutic targets for Parkinson's disease: a possible link between Lewy pathology and membrane...

Pathologically, Parkinson's disease (PD) is characterized by nigral cell loss and Lewy pathology in the remaining neurons. Whereas the motor symptoms of PD show a marked response to dopamine replacement therapy, many of the non-motor symptoms are resistant to treatment. This suggests that in addition to nigral cell loss, widespread Lewy pathology in the nervous system is associated with the manifestations of PD. Areas covered: Although the mechanism of Lewy body formation remains largely unknown, it is becoming clear that changes in the behavior of α-synuclein are critical in this process. α-Synuclein behaves differently depending on the lipid composition of membranes with which it interacts; therefore, one can postulate that the altered lipid composition of neuronal membranes may lead to Lewy pathology. The lipid composition of cellular membranes is consistently altered in the brains of patients with PD, and Lewy pathology is a common feature of several human lipidoses with mutations in enzymes that affect membrane lipids. This further supports the concept that alterations in the membrane lipids of neurons are central to Lewy pathology. Expert opinion: This concept provides a new platform to establish models for the development of novel treatments for PD.