Lipid peroxidation is essential for α‐synuclein‐induced cell death
Although Parkinson’s disease is a complex multifactorial disorder, one key causal factor remains the misfolding and aggregation of the protein α‐Syn. The major histopathological hallmarks of Parkinson’s Disease (PD) include the loss of dopaminergic neurons in substantia nigra and the presence of Lewy bodies, which are intracellular inclusions of aggregated α‐Syn. The exact mechanism by which aggregation of α‐Syn induces neuronal cell death in the course of the disease is not yet clear; however, a growing body of evidence points towards a key role of oxidative stress in PD pathogenesis (Gandhi and Abramov 2012).
Reactive oxygen species (ROS) and even mild lipid peroxidation have been shown to play important roles in physiological signal transduction (Vaarmann et al. 2010; Domijan et al. 2014), but overproduction of ROS may lead to oxidative damage to DNA, proteins and/or to lipid membranes. The extent of tissue damage through oxidation depends on the tissue composition and on the ability of the intracellular antioxidant system to restore ROS production to basal levels. The brain is particularly prone to oxidative damage, due to the high level of oxidation‐prone polyunsaturated fatty acids (PUFAs), high rates of ROS production due to high oxygen consumption and energy turnover and low levels of endogenous antioxidants (Halliwell 2006). Twenty per cent of all energy generated by the body is utilized by the brain, of which a striking 25% (i.e. the 5% of the total energy generated) is spent on maintaining and repairing oxidatively damaged lipid membranes (Brenna and Carlson 2014).