Role of Environmental and Inflammatory Toxicity in Neuronal Cell Death

Neuronal cells are exclusively dependent on oxidative phosphorylation for energy and are under constant threat of oxidative damage due to mitochondrial production of reactive oxygen species by partial reduction of molecular oxygen. These cells also have a multitude of antioxidative defense mechanisms, but there is a slow decline of antioxidative de- fence capacity with aging. The result is the increased vulnerability of cells to oxidative stress, particularly neuronal cells. Any environmental, inflammatory or psychological stress that can topple the redox balance will eventually lead to oxida- tive stress and neuronal cell death. Indeed, cell death induced by oxidative stress has been implicated in age-related loss of neurons during normal aging and several neurodegenerative disorders. It is critical to understand the mechanisms by which different risk factors lead to neuronal cell death in order to identify pathways involved in neurodegenerative dis- eases. In this review we focus on the implications of various factors such as environmental toxins, drugs and psychologi- cal stress in neurodegenerative diseases with specific focus on Parkinson's disease and Alzheimer's disease. Here we highlight the recent progress that supports the role of molecular mechanisms of oxidative stress, neuroinflammation and mitochondrial dysfunction as contributors to neurotoxicity and research on developing therapeutics that could potentially slow down the progression of neurodegeneration.