Pathophysiology and Therapeutic Perspectives of Oxidative Stress and Neurodegenerative Diseases: A Narrative Review

Abstract

Introduction: Neurodegeneration is the term describing the death of neurons both in the central nervous system and periphery. When affecting the central nervous system, it is responsible for diseases like Alzheimer's disease, Parkinson's disease, Huntington's disorders, amyotrophic lateral sclerosis, and other less frequent pathologies. There are several common pathophysiological elements that are shared in the neurodegenerative diseases. The common denominators are oxidative stress (OS) and inflammatory responses. Unluckily, these conditions are difficult to treat. Because of the burden caused by the progression of these diseases and the simultaneous lack of efficacious treatment, therapeutic approaches that could target the interception of development of the neurodegeneration are being widely investigated. This review aims to highlight the most recent proposed novelties, as most of the previous approaches have failed. Therefore, older approaches may currently be used by healthcare professionals and are not being presented. Methods: This review was based on an electronic search of existing literature, using PubMed as primary source for important review articles, and important randomized clinical trials, published in the last 5 years. Reference lists from the most recent reviews, as well as additional sources of primary literature and references cited by relevant articles, were used. Results: Eighteen natural pharmaceutical substances and 24 extracted or recombinant products, and artificial agents that can be used against OS, inflammation, and neurodegeneration were identified. After presenting the most common neurodegenerative diseases and mentioning some of the basic mechanisms that lead to neuronal loss, this paper presents up to date information that could encourage the development of better therapeutic strategies. Conclusions: This review shares the new potential pharmaceutical and not pharmaceutical Enhanced Digital Features To view enhanced digital features for this article go to

Inhibition of microRNA-155 Protects Retinal Function Through Attenuation of Inflammation in Retinal Degeneration

“…Typically, regulation of mRNAs by a mature miRNA occurs through incorporation into Argonaute (AGO) proteins, most commonly AGO2, of the RNA-induced silencing complex (RISC) [2][3][4]. Although the mechanism of miRNA regulation and their targets under different biological and pathological conditions are still being elucidated, miRNAs have the capacity to simultaneously repress multiple mRNA targets within a specific process, such as oxidative stress and cellular inflammation [5,6]. They are therefore ideal therapeutic targets for controlling dysregulated or overactive biological pathways [7,8], such as occurs in retinal degenerations including agerelated macular degeneration (AMD).…”

Vasopressor-Sparing Action of Methylene Blue in Severe Sepsis and Shock: A Narrative Review

“…nNOS is found primarily in the brain and spinal cord where it modulates learning, neurogenesis, memory, and regulates blood pressure. Very recent evidence suggests a pivotal role of abnormal NO signaling and oxidative stress mediated by neuroinflammation in the pathogenesis of neurodegenerative diseases [ 14 , 16 ]. eNOS exists primarily in endothelial cells, but also occurs in other cell types including platelets and cardiac myocytes.…”

“…Redundant activation of the NO–cGMP pathway has been associated with distributive shock such as sepsis and anaphylaxis [ 14 , 19 ]. However, NO may exert protective effects through its capacity to counteract oxidative stress [ 16 ], extinguish apoptosis, prevent platelet and leukocyte adhesion, induce anti-inflammatory activity, and kill pathogens [ 14 , 17 ]. This dual personality of NO can help to explain why unselective NOS inhibitors fail to provide clinical benefits in patients with sepsis [ 14 ].…”

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“…According to this consensus, oxidative damage in the brain of patients is resultant from excessive production of free radicals induced by fragments of insoluble and/or overproduced proteins, such as β-amyloid peptide, α-synuclein, tau and huntingtin, with functional alteration in the mitochondria, inadequate energy supply, production of inflammatory mediators and alteration of antioxidant defenses (Islam, 2016;Liu et al, 2017). Thus, the modulation of the cellular oxidative process should lead to a new concept in the design of drugs and, possibly, a new way of searching for more effective disease-modifying chemical entities, reinforcing the hope of at least real clinical relief, if healing is not yet possible (Ghosh et al, 2011;Rekatsina et al, 2020).…”