Lipids at the crossroad of α-synuclein function and dysfunction: Biological and pathological implications

Abstract

Since its discovery, the study of the biological role ofα-synuclein and its pathologicalimplications has been the subject of increasing interest. The propensity to adoptdifferent conformational states governing its aggregation and fibrillation makes thissmall 14-kDa cytosolic protein one of the main etiologic factors associated withdegenerative disorders known as synucleinopathies. The structure, function, and toxicityofα-synuclein and the possibility of different therapeutic approaches to target theprotein have been extensively investigated and reviewed. One intriguing characteristic ofα-synuclein is the different ways in which it interacts with lipids. Though in-depth studieshave been carried out in this field, the information they have produced is puzzling andthe precise role of lipids inα-synuclein biology and pathology andvice versais still largelyunknown. Here we provide an overview and discussion of the main findings relating toα-synuclein/lipid interaction and its involvement in the modulation of lipid metabolismand signaling.