Mechanism of Oxidative Stress in Neurodegeneration

By S. Gandhi, A. Abramov. Oxidative Medicine and Cellular Longevity, 2012

925 citations recorded by the source corpus.

Biological tissues require oxygen to meet their energetic demands. However, the consumption of oxygen also results in the generation of free radicals that may have damaging effects on cells. The brain is particularly vulnerable to the effects of reactive oxygen species due to its high demand for oxygen, and its abundance of highly peroxidisable substrates. Oxidative stress is caused by an imbalance in the redox state of the cell, either by overproduction of reactive oxygen species, or by dysfunction of the antioxidant systems. Oxidative stress has been detected in a range of neurodegenerative disease, and emerging evidence from in vitro and in vivo disease models suggests that oxidative stress may play a role in disease pathogenesis. However, the promise of antioxidants as novel therapies for neurodegenerative diseases has not been borne out in clinical studies. In this review, we critically assess the hypothesis that oxidative stress is a crucial player in common neurodegenerative disease and discuss the source of free radicals in such diseases. Furthermore, we examine the issues surrounding the failure to translate this hypothesis into an effective clinical treatment.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/5877b9b7cc7819ce799d51b83da0764cb214c464

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Plamena R. Angelova
2. A. Abramov
3. E. Sanz
4. I. Peluso
5. Hugo J. Bellen
6. M. Iriti

In Physiology

1. A. Abramov
2. I. Peluso
3. M. Iriti

Citations in the corpus

• The oxidative stress hypothesis in Alzheimer's disease. (2013, background): “This group expresses higher concentrations of antioxidants and also genes involved in oxidative stress (Gandhi et al. 2012).”
• Oxidative Stress and the Central Nervous System (2017, neutral): “Neurodegenerative disorders commonly associatedwithmuscular, dementic, and cognitive deficits exhibit brain atrophy, neurofibrillary tangles, plaques, and aggregates as pathologic hallmarks of the disease (Kipps et al., 2005; Obeso et al., 2008; Gandhi and Abramov, 2012).”
• The Role of Oxidative Stress in Neurodegenerative Diseases (2015, background): “In normal conditions, the enzyme is present as a form of XDH [2].”
• Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution (2024, background): “However, some fundamental differences have been revealed from fish to mammals—for example, the ROS-responsive D-box-mediated transcription we discussed in this review.”
• Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases (2020, background): “In the pathogenesis of neurodegeneration, many processes are included, such as protein misfolding and aggregation, abnormal kinase-signaling pathways, neuronal calcium dysregulation, and even impaired synaptic transmission (Gandhi and Abramov, 2012).”
• Role of mitochondrial ROS in the brain: from physiology to neurodegeneration (2018, background): “[25] Gandhi S & Abramov AY (2012) Mechanism of oxidative stress in neurodegeneration.”
• Glial Lipid Droplets and ROS Induced by Mitochondrial Defects Promote Neurodegeneration (2015, positive): “In the clinical setting, the prescription of antioxidants towards treatment of neurodegenerative diseases has been tested repeatedly on patients with neurodegenerative disorders (Galasko et al., 2012; Gilgun-Sherki et al., 2001; Gandhi and Abramov, 2012), without compelling results.”