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.
Highlights
The endoplasmic reticulum (ER), which has a higher ratio of oxidation similar to extracellular space, is the main component of protein folding in eukaryotic cells, and ER-associated degradation plays a crucial role in preventing protein accumulation and aggregation [38]
Several miRNAs can be oxidized themselves and regulate the expression levels of many genes involved in antioxidant defense pathways [63]; for example, oxidative modification of miR-184 reduced expression levels of Bcl-xL and Bcl-w due to misrecognitions, leading to apoptosis [64], and miR-27a influences redox homeostasis due to reduced expression levels of nuclear factor E2-related factor 2 (NRF2), which is a major regulator of antioxidant elements [65]
We summarize currently established knowledge regarding oxidative biomolecular modifications and promising biomarker candidates linked to oxidative stress in Amyotrophic lateral sclerosis (ALS)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Several types of reactive species, including reactive oxygen species (ROS), reactive nitrogen species, and reactive sulfur species, are essential factors in redox signaling in biology [1,2] These reactive species are produced by cellular homeostatic metabolism and exogenous pro-oxidant factors, including environmental and atmospheric pollution, heavy metals, or tobacco [3]. Among these reactive species, two ROS species, hydrogen peroxide (H2 O2 ) and superoxide anion radical (O2 − ), are key redox signaling agents generated under the tight control of growth factors and cytokines by over 40 enzymes [4]. We discuss promising biomarker candidates linked to oxidative stress in ALS
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