Is Modulation of Oxidative Stress an Answer? The State of the Art of Redox Therapeutic Actions in Neurodegenerative Diseases

Abstract

The central nervous system is particularly sensitive to oxidative stress due to many reasons, including its high oxygen consumption even under basal conditions, high production of reactive oxygen and nitrogen species from specific neurochemical reactions, and the increased deposition of metal ions in the brain with aging. For this reason, along with inflammation, oxidative stress seems to be one of the main inducers of neurodegeneration, causing excitotoxicity, neuronal loss, and axonal damage, ultimately being now considered a key element in the onset and progression of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and hereditary spastic paraplegia. Thus, the present paper reviews the role of oxidative stress and of its mechanistic insights underlying the pathogenesis of these neurodegenerative diseases, with particular focus on current studies on its modulation as a potential and promising therapeutic strategy.

Figure 1

Cross talk between oxidative stress, inflammation, and neurodegeneration. The different reactive species are produced by several cell types, either by resident brain cells (i.e., glia) or by infiltrated leukocytes (i.e., monocytes/macrophages and dendritic cells), and affect both inflammatory processes, by enhancing cytokine release from proinflammatory T cells, and neurodegeneration, by inducing neuronal cell death and axonal loss. ^•O₂ ⁻: superoxide radical anion; HO^•: hydroxyl radical; ROO^•: peroxyl radical; HO₂ ^•: hydroperoxyl radical; H₂O₂: hydrogen peroxide; NO^•: nitric oxide; Th: T-helper.