A Review of Oxidative Stress Products and Related Genes in Early Alzheimer’s Disease

Abstract

Oxidative stress is associated with the progression of Alzheimer’s disease (AD). Reactive oxygen species can modify lipids, DNA, RNA, and proteins in the brain. The products of their peroxidation and oxidation are readily detectable at incipient stages of disease. Based on these oxidation products, various biomarker-based strategies have been developed to identify oxidative stress levels in AD. Known oxidative stress-related biomarkers include lipid peroxidation products F2-isoprostanes, as well as malondialdehyde and 4-hydroxynonenal which both conjugate to specific amino acids to modify proteins, and DNA or RNA oxidation products 8-hydroxy-2’-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG), respectively. The inducible enzyme heme oxygenase type 1 (HO-1) is found to be upregulated in response to oxidative stress-related events in the AD brain. While these global biomarkers for oxidative stress are associated with early-stage AD, they generally poorly differentiate from other neurodegenerative disorders that also coincide with oxidative stress. Redox proteomics approaches provided specificity of oxidative stress-associated biomarkers to AD pathology by the identification of oxidatively damaged pathology-specific proteins. In this review, we discuss the potential combined diagnostic value of these reported biomarkers in the context of AD and discuss eight oxidative stress-related mRNA biomarkers in AD that we newly identified using a transcriptomics approach. We review these genes in the context of their reported involvement in oxidative stress regulation and specificity for AD. Further research is warranted to establish the protein levels and their functionalities as well as the molecular mechanisms by which these potential biomarkers are involved in regulation of oxidative stress levels and their potential for determination of oxidative stress and disease status of AD patients.

Gut microbiota may be involved in Alzheimer’s disease pathology by dysregulating pyrimidine metabolism in APP/PS1 mice

“…Also, inflammatory or Aβ-associated bacteria such as Erysipelotrichaceae ( Bäuerl et al, 2018 ; Ticinesi et al, 2019 ) and Proteobacteria ( Nagpal et al, 2019 ; Ticinesi et al, 2019 ; Nagu et al, 2021 ) increased in APP/PS1 mice, which play key roles in the pathogenesis of AD. Similarly, some differential metabolites have been reported to be AD-related, such as 8-hydroxy-2-deoxyguanosine, a marker of nucleic acid oxidation ( Mecocci et al, 2018 ; Cioffi et al, 2021 ), and beneficial substances, including 15-oxoETE ( Snyder et al, 2015 ), 12-oxo-9(Z)-dodecenoic acid ( Yang et al, 2021 ), arbutin ( Dastan et al, 2019 ), 18β-glycyrrhetinic acid ( Wagle et al, 2018 ), and n -oleoylethanolamine ( Xu et al, 2016 ). Here, several previously unidentified differential bacteria and fecal metabolites were discovered, and their roles in AD need to be explored in further studies.…”

Metabolomic Footprint of Disrupted Energetics and Amino Acid Metabolism in Neurodegenerative Diseases: Perspectives for Early Diagnosis and Monitoring of Therapy

“…An inversely proportional concentration of 8-OHG to the concentration of Aβ was observed. In addition, the levels of these compounds were five times higher than those of healthy subjects [ 106 ].…”

From Small Peptides to Large Proteins against Alzheimer’sDisease

“…Indeed, oxidatively changed nucleic acid and protein products, as well as products of lipid peroxidation and glycoxidation, are recognized as markers of oxidative harm [ 81 ]. Several markers have been found in the afflicted lesions of patients with these disorders in postmortem brain tissue or pre-mortem cerebrospinal fluid, plasma, serum, and urine [ 82 ]. When reactive oxygen species, particularly hydroxyl radicals, attack DNA, they can cause strand breakage, DNA-DNA and DNA-protein cross-linking, sister chromatid exchange and translocation, and the production of at least 20 oxidized base adducts.…”