Biomolecular Modifications Linked to Oxidative Stress in Amyotrophic Lateral Sclerosis: Determining Promising Biomarkers Related to Oxidative Stress

Abstract

Reduction–oxidation reactions are essential to cellular homeostasis. Oxidative stress transcends physiological antioxidative system damage to biomolecules, including nucleic acids and proteins, and modifies their structures. Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. The cells present in the central nervous system, including motor neurons, are vulnerable to oxidative stress. Neurodegeneration has been demonstrated to be caused by oxidative biomolecular modifications. Oxidative stress has been suggested to be involved in the pathogenesis of ALS. Recent progress in research on the underlying mechanisms of oxidative stress in ALS has led to the development of disease-modifying therapies, including edaravone. However, the clinical effects of edaravone remain limited, and ALS is a heretofore incurable disease. The reason for the lack of reliable biomarkers and the precise underlying mechanisms between oxidative stress and ALS remain unclear. As extracellular proteins and RNAs present in body fluids and represent intracellular pathological neurodegenerative processes, extracellular proteins and/or RNAs are predicted to promise diagnosis, prediction of disease course, and therapeutic biomarkers for ALS. Therefore, we aimed to elucidate the underlying mechanisms between oxidative stress and ALS, and promising biomarkers indicating the mechanism to determine whether therapy targeting oxidative stress can be fundamental for ALS.

Values of Nitric Oxide and Superoxide Dismutase in Cerebrospinal Fluid of Patients with Sporadic Amyotrophic Lateral Sclerosis

“…Oxidative stress might be both a cause and consequence of the disease and is associated with pathogenesis as well as disease progression (Ikawa et al 2015). Given the higher incidence of the disease in men, some studies have investigated the vulnerability of the male and female nervous systems to OS and neurotoxic effects (Takashi et al, 2021).…”

New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases

“…Moreover, Edaravone, a drug approved in the USA for alleviating ALS symptoms, involved in lipid peroxides and hydroxyl radical elimination, is not particularly effective in disease treatment [ 137 ]. In 2019, Walczak and co-authors compared ALS patients and control subjects in terms of mitochondrial function and antioxidant enzymes, and they found a decreased expression in ALS patients’ mitochondria complexes I, II, III, and IV proteins; in mitochondrial membrane potential; and in SOD1 and catalase, both antioxidant enzymes [ 138 ]. In addition, ALS patients carrying mutations in CHCHD10 , involved in ALS pathology and in mitochondrial cristae morphology maintenance, manifest fibroblasts with mitochondrial damage and mitochondrial network fragmentation [ 139 ].…”

Perineuronal nets are phagocytosed by MMP‐9 expressing microglia and astrocytes in the SOD1G93A ALS mouse model

“…We, therefore, investigated the levels of oxidative stress in α-MNs during disease progression in SOD1 G93A mice compared with age-match WT mice. The expression of oxidative stress markers 3-nitrotyrosine (3-NT) and 8-oxo-2 0 -deoxyguanosine (8-oxo-dG), which indicate protein [61] and DNA oxidation [62], respectively, were investigated in α-MNs. 3-NT fluorescence intensity was shown to be significantly increased in the α-MNs of onset stage SOD1 G93A mice (2.813 ± 0.5520, n = 7) compared with WT (1.000 ± 0.9005, p < 0.05, n = 7; Figure 7A-D).…”