α-Synuclein and Polyunsaturated Fatty Acids: Molecular Basis of the Interaction and Implication in Neurodegeneration

α-Synuclein (α-syn) is a 140-amino acid protein, the physiological function of which has yet to be clarified. It is involved in several neurodegenerative disorders, and the interaction of the protein with brain lipids plays an important role in the pathogenesis of Parkinson’s disease (PD). Polyunsaturated fatty acids (PUFA) are highly abundant in the brain where they play critical roles in neuronal membrane fluidity and permeability, serve as energy reserves and function as second messengers in cell signaling. PUFA concentration and composition in the brain are altered with age when also an increase of lipid peroxidation is observed. Considering that PD is clearly correlated with oxidative stress, PUFA abundance and composition became of great interest in neurodegeneration studies because of PUFA’s high propensity to oxidize. The high levels of the PUFA docosahexaenoic acid (DHA) in brain areas containing α-syn inclusions in patients with PD further support the hypothesis of possible interactions between α-syn and DHA. Additionally, a possible functional role of α-syn in sequestering the early peroxidation products of fatty acids was recently proposed. Here, we provide an overview of the current knowledge regarding the molecular interactions between α-syn and fatty acids and the effect exerted by the protein on their oxidative state. We highlight recent findings supporting a neuroprotective role of the protein, linking α-syn, altered lipid composition in neurodegenerative disorders and PD development.