Isotopic reinforcement of essential polyunsaturated fatty acids diminishes nigrostriatal degeneration in a mouse model of Parkinson’s disease
Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting 1–2% of the population over 65 years of age. A role for oxidative stress in PD etiology is supported by a vast literature, including evidence of polyunsaturated fatty acid (PUFA) peroxidation products, including 4-hydroxynonenal (HNE) and malondialdehyde (MDA), the major products of PUFA oxidation in post-mortem tissue for patients with PD. Furthermore, oxidized PUFA initiate further cellular injury through oxidation of DNA, proteins and other cellular targets, including those linked to PD: dopamine (DA) and importantly alpha-synuclein. PUFA are essential components that make up a substantial fraction of lipid membranes. PUFA, specifically linoleic (LA; 18:2n − 6) and -linolenic (ALA; 18:3n − 3) acids, are early targets of oxidation by reactive oxygen species (ROS) (Fig. 1). This damage deteriorates the properties of lipid membranes such as fluidity (Dobretsov et al., 1977). Moreover, oxidized PUFA can damage other biomolecules, most notably proteins and DNA, through reactive carbonyl products (RCP) suchasHNE, 4-hydroxyhexenal(HHE),malondialdehyde (MDA) and acrolein (Lim et al., 2004).