Role of Oxidative Stress, ER Stress and Ubiquitin Proteasome System in Neurodegeneration

Neurodegenerative disorders (NDDs) are progressive and chronic disorders characterized by destruction of neurons in sensory, motor and cognitive systems. Free radical’s accumulation, oxidative stress, ER stress and a dysfunctional ubiquitin proteasome system can regulate prognosis in NDDs. Oxidative trauma in the brain can result from high rate of oxidative metabolism in contrast to the diminished functional levels of the antioxidant enzymes responsible for detoxification. Endoplasmic Reticulum (ER) advocates a degree of control on cellular parameters such as proper protein folding, posttranslational modification and subsequent protein trafficking in order to maintain normal cellular homeostasis. However, an abnormal ER functioning can lead to loss of integrity of the ER thus resulting in ER stress. In addition to this impairment in the ubiquitin proteasome system (UPS) machinery results in the accumulation of toxic proteins in the brain thus resulting in severe neuronal trauma and subsequent damage. This review explores the disease critical interactions and roles of three critical NDD determinants viz. oxidative stress, ER stress and UPS dysfunction in neurodegenerative conditions.