Epigenetic Effects Induced by Methamphetamine and Methamphetamine-Dependent Oxidative Stress

Figure 5

METH induces oxidative stress within DA terminals. Toxic DA by-products (quinones and DOPALD) together with highly reactive species such as H₂O₂ and reactive oxygen species (ROS) react with sulfhydryl groups and promote structural modifications of proteins within the DA axon terminals. The enhanced redox imbalance also disrupts the homeostasis of endoplasmic reticulum (ER) and mitochondria, which further accelerates the production of ROS. Thus, an excessive amount of misfolded/insoluble proteins and damaged organelles occurs, which leads to an engulfment of autophagy (ATG) and ubiquitin proteasome (UP) cell-clearing systems. These events converge in producing neurotoxicity within DA terminals, which may either extend to DA cell bodies.