Role of oxidative stress in neurodegenerative disorders: a review of reactive oxygen species and prevention by antioxidants

Abstract

Neurological disorders include a variety of conditions, Alzheimer’s disease, Motor Neuron disease, and Parkinson’s disease, affecting longevity and quality of life and their pathogenesis is associated with oxidative stress. Several of the chronic neurodegenerative pathologies of the central nervous system share some common features, such as, oxidative stress, inflammation, synapse dysfunctions, protein misfolding, and defective autophagia. Neuroinflammation can involve the activation of mast cells, contributing to oxidative stress, in addition other the sources of reactive oxygen species. Antioxidants can powerfully neutralise reactive oxygen species and free radicals, decreasing oxidative damage. Antioxidant genes, like manganese superoxide dismutase enzyme, can undergo epigenetic changes that reduce their expression, thus increasing oxidative stress in tissue. Alternatively, DNA can be altered by free radical damage. The epigenetic landscape of these genes can change antioxidant function and may result in neurodegenerative disease. This imbalance of free radical production and antioxidant function increases the reactive oxygen species that cause cell damage in neurons and is often observed as an age-related event. Increased antioxidant expression in mice is protective against reactive oxygen species in neurons as is the exogenous supplementation of antioxidants. Manganese superoxide dismutase requires manganese for its enzymic function. Antioxidant therapy is considered for age-related neurodegenerative diseases and new mimetic of a manganese superoxide dismutase, Avasopasem Manganese is described and suggested as putative treatment to reduce the oxidative stress that causes neurodegenerative disease. The aim of this narrative review is to explore the evidence that oxidative stress causes neurodegenerative damage and the role of antioxidant genes in inhibiting reactive oxygen species damage. Can the neuronal environment of oxidative stress, causing neuroinflammation and neurodegeneration, be reduced or reversed?

Transcriptome Study of rd1Mouse Brain and Association with Parkinson’s Disease

“…The KEGG pathway involving intersecting DEGs includes pathway of neurodegeneration-multiple diseases, Alzheimer's disease (AD), diabetic cardiomyopathy, chemical carcinogenesis-reactive oxygen species, HIF-1 signaling pathway, dopaminergic synapse, and central carbon metabolism in cancer (Figure G). The inflammatory hypothesis has been proposed to explain the pathogenesis of neurodegenerative diseases . It has been demonstrated that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is expressed in activated microglia in the retinas of rd1 mice.…”

Ergothioneine Prevents Neuronal Cell Death Caused by the Neurotoxin 6-Hydroxydopamine

“…These previous studies support our proposition that ergothioneine, which can inhibit excessive ROS production or oxidative stress, may be a way to prevent the development and exacerbation of PD. Furthermore, as oxidative stress is a cause of the onset and exacerbation of various diseases, such as other neurological diseases and diabetes [41,42], it is expected that ergothioneine can be applied as a preventive method for other diseases.…”

Pathogenetic Contributions and Therapeutic Implications of Transglutaminase 2 in Neurodegenerative Diseases

“…(2) interventions that reduce oxidative stress or other cellular stressors and may indirectly curtail TG2 activity, such as antioxidant agents ethyl pyruvate, N-acetylcysteine (NAC), and α-Lipoic Acid [51,[73][74][75]; and (3) the possible exploration of the genetic modulation of TG2 expression, including gene-silencing techniques and CRISPR/Cas9 gene editing to regulate TG2 levels [76][77][78]. However, the feasibility and safety of the latter approaches need thorough investigation [78].…”