Oxidative stress in neurodegeneration and available means of protection

Abstract

Substantial pieces of direct and indirect evidence have mounted over the years linking the induction of oxidative stress to a plethora of disease conditions, not least those associated with the death of neurons. The causal relationship between oxidative damage and neurodegeneration is, however, not yet clear and still a subject of intense investigation. Nevertheless, the phenomenon of oxidative neuronal death has received considerable attention in a frantic search for efficacious therapies for the management of neurological and neurodegenerative conditions. The redox-active nature of reactive oxygen species (ROS), which in their excessive levels induce oxidative stress, the prevalence of ROS production in biological systems, the complexity of interrelationships among these species, and the context-dependent adequacy and resilience of the antioxidant defense systems are some of the challenges that basic research has to grapple with to advance successfully to the translational stage. Much still has to be understood for research efforts in this field to yield enduring therapies. In this review, we examine the nature (chemistry) of ROS, the relationships between them, their physiological functions, the roles of oxidative stress in neurodegeneration, the mechanisms of cell death induced by oxidant species, and the available means of protecting neurons against oxidative damage.

Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage

“…Neurons likely produce high levels of ROS and contain relatively fewer antioxidant molecules (Cui et al, 2004;Fatokun et al, 2008). Consistent with the vulnerability of Purkinje cells to mitochondrial division deficiency, these cells are one of the largest neurons and maintain exceptionally abundant connections with other neurons, thereby leading to a high metabolic demand and high levels of ROS (Kern and Jones, 2006).…”

The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein

“…Oxidative stress is a common promoter of neurodegeneration 18 , raising the question of its possible involvement in the toxicity of GD ligands. Indeed, the reactive oxygen species (ROS) scavengers, ascorbate (0.1-2.5 mM) and N-acetyl cysteine, conferred neuroprotection against POM1-mediated toxicity (Fig.…”

Evidence of Oxidative Injury of the Spinal Cord in 2 Horses With Equine Degenerative Myeloencephalopathy

“…12 Some oxygen metabolites, such as superoxide radical, hydrogen peroxide, and hydroxyl radical, serve as potent oxidants capable of causing cellular injury and lipid peroxidation. 7 These reactive oxygen species are associated with local cellular injury; however, breakdown products produced during lipid peroxidation create lipid peroxides, such as 4-HNE, malonaldehyde, acrolein, and hexanal; diffuse from their site of origin; and may have toxic and reactive properties. 10 Hydroxynonenal is a major product of unsaturated aldehyde formed during oxidative stress due to lipid peroxidation and is widely used as a marker of membrane lipid peroxidation.…”