Deuterium‐reinforced polyunsaturated fatty acids improve cognition in a mouse model of sporadic Alzheimer’s disease
Oxidative damage due to increased oxidative stress is considered an important factor in the pathogenesis of Alzheimer’s disease (AD) and other neurodegenerative diseases including retinal diseases, Parkinson’s disease (PD), and Huntington’s disease. High brain levels of polyunsaturated fatty acids (PUFAs) and transition metals, coupled with high oxygen utilization and modest antioxidant defense, creates an environment especially vulnerable to oxidative damage. Oxidative damage is present in the very early stages of AD suggesting it is a primary driving force in AD pathogenesis.
Reactive oxygen species (ROS)‐initiated nonenzymatic lipid peroxidation (LPO) of PUFAs such as linoleic (LA), linolenic (ALA), arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids is the major contributor to oxidative damage, resulting in altered membrane fluidity and changes in membrane‐bound enzymes and receptors. LPO of PUFAs by ROS is initiated by abstraction of bis‐allylic hydrogens, generating resonance‐stabilized free radicals which subsequently react with molecular oxygen to form lipid peroxyls. These newly formed species abstract a hydrogen atom off an adjacent PUFA molecule thus propagating the chain reaction. Propagation is eventually terminated by a chain‐terminating antioxidant such as vitamin E or by homologous recombination.