The Central Role of Biometals Maintains Oxidative Balance in the Context of Metabolic and Neurodegenerative Disorders

Figure 3

The causative mechanisms of the pathological elevation of nitrosative/oxidative species and their abilities to modify relevant proteins associated with the pathogenesis of neurodegenerative diseases. The activation of iNOS by inflammatory processes and of nNOS by Ca²⁺ influx through NMDAR leads to an increase in intracellular levels of RNS. On the other hand, ROS is generated upon mitochondrial dysfunction, and endoplasmic reticulum (ER) stress is a result of dopamine metabolism by monoamine oxidase (MAO). Hypoxic conditions and toxic compounds, such as rotenone and MPTP, are also considered as carriers of harmful effects to the physiology of the mentioned organelles. However, rotenone and MPTP also exert stimulatory effects on iNOS. Damaged and aggregated proteins create a solid base on which to create a vicious cycle by the strengthening of iNOS activity and by the deepening of mitochondrial and ER dysfunctioning.