Neuroprotective Role of N-acylphosphatidylethanolamines in Parkinson's Disease

N-acylphosphatidylethanolamines are a class of phospholipids present at low concentrations in cellular membranes1. They have been studied as fatty-acid ethanolamine (FAEs) precursors, given FAEs bioactive effects such as control of inflammation2, pain sensation and neuroprotection3 as well as control of food intake4. However, NAPEs may also have biological functions of their own: they might participate in the control of membrane fluidics5, organization of lipid raft5, arrangement of cell division site domains7 and protein anchorage. Evidence indicates that NAPEs are produced in the brain following injurious stimuli of diverse nature. In this context, we have recently observed that this lipid molecules are increased following the administration of the neurotoxin 6-hydroxydopamine in mice13, a widely used model of Parkinson's disease. Parkinson's disease is a chronic progressive neurodegenerative disease caused by the loss of the nigrostriatal dopaminergic neurons14, which results in an impairment of the control of voluntary movements, leading to a motor symptomatology. Parkinson's disease represents a substantial burden for public health. Unfortunately to date no therapies have been developed to cure neurodegenerative disease. Thus, there is the need to understand in greater depth Parkinson's disease pathophysiology and to further develop new therapeutic approaches for this condition. The aim of the present work was to elucidate whether and how NAPE production is involved in the neurodegenerative process. Using a combination of genetic, pharmacological and behavioral techniques, I showed that locally produced NAPEs exert protective effects against 6-OHDA-induced toxicity by regulating the expression and activity of LRRK2, a multifunctional protein that is known to be involved in both familial and sporadic Parkinson's. The evidence collected in my experiments may thus provide a starting point for the development of new therapeutic approaches for neurodegenerative disease, as well as for the identification of biological markers useful in the early detection of these pathological diseases.