Role of oxidative stress and mitochondrial dysfunction in neurodegenerative disorders

Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are characterized by the progressive decline of neuronal structure and function, resulting in significant cognitive and motor impairments. This chapter explores the intricate roles of oxidative stress and mitochondrial dysfunction in the onset and advancement of these conditions. Oxidative stress occurs when there is an imbalance between the generation of reactive oxygen species (ROS) and the body's ability to counteract them with antioxidants, leading to damage of proteins, lipids, and nucleic acids within neurons. Mitochondria, vital organelles responsible for energy production, calcium regulation, and synaptic function, are major producers of ROS and primary targets of oxidative damage. When mitochondrial function is compromised, it exacerbates oxidative stress, creating a detrimental cycle that promotes neuronal death through regulated cell death pathways such as apoptosis, necroptosis, and autophagy. This chapter delves into the mechanisms linking oxidative stress and mitochondrial dysfunction, including activating proapoptotic signaling pathways, disrupting mitochondrial quality control processes such as mitophagy, and initiating neuroinflammatory responses. It illustrates how these interconnected processes manifest in neurodegenerative diseases, emphasizing the consequences of impaired mitochondrial dynamics on neuronal survival and functionality. Therapeutic strategies targeting these challenges are evaluated focusing on antioxidant interventions and the restoration of cellular homeostasis and mitigating neuronal degeneration.