The Underlying Role of Oxidative Stress in Neurodegeneration: A Mechanistic Review

Yaribeygi, Habib; Panahi, Yunes; Javadi, Behjat; Sahebkar, Amirhossein

doi:10.2174/1871527317666180425122557

Cited by 133 publications

(101 citation statements)

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“…However, oxidative stress, especially when caused by mitochondrial malfunction, can also induce inflammatory responses. The pivotal role of oxidative stress in these pathologies has been recently reviewed . Melatonin is a broad‐spectrum antioxidant that acts by various mechanisms that comprise direct and indirect detoxification of free radicals, mitochondrial protection, reduction of free radical formation by inhibiting electron leakage and NADPH oxidases, prevention of neuronal overexcitation and several anti‐inflammatory actions .…”

Section: Melatonin and Inflammation In Neurodegenerative Diseasesmentioning

confidence: 99%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

360

350

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Melatonin is an immune modulator that displays both pro‐ and anti‐inflammatory properties. Proinflammatory actions, which are well documented by many studies in isolated cells or leukocyte‐derived cell lines, can be assumed to enhance the resistance against pathogens. However, they can be detrimental in autoimmune diseases. Anti‐inflammatory actions are of particular medicinal interest, because they are observed in high‐grade inflammation such as sepsis, ischemia/reperfusion, and brain injury, and also in low‐grade inflammation during aging and in neurodegenerative diseases. The mechanisms contributing to anti‐inflammatory effects are manifold and comprise various pathways of secondary signaling. These include numerous antioxidant effects, downregulation of inducible and inhibition of neuronal NO synthases, downregulation of cyclooxygenase‐2, inhibition of high‐mobility group box‐1 signaling and toll‐like receptor‐4 activation, prevention of inflammasome NLRP3 activation, inhibition of NF‐κB activation and upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2). These effects are also reflected by downregulation of proinflammatory and upregulation of anti‐inflammatory cytokines. Proinflammatory actions of amyloid‐β peptides are reduced by enhancing α‐secretase and inhibition of β‐ and γ‐secretases. A particular role in melatonin's actions seems to be associated with the upregulation of sirtuin‐1 (SIRT1), which shares various effects known from melatonin and additionally interferes with the signaling by the mechanistic target of rapamycin (mTOR) and Notch, and reduces the expression of the proinflammatory lncRNA‐CCL2. The conclusion on a partial mediation by SIRT1 is supported by repeatedly observed inhibitions of melatonin effects by sirtuin inhibitors or knockdown.

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Section: Melatonin and Inflammation In Neurodegenerative Diseasesmentioning

confidence: 99%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

360

350

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“…It plays a significant role in the pathogenesis and pathophysiology of different diseases, including cardiovascular, neurodegenerative, oncological, inflammatory, etc. (22,23). Thus, the role of antioxidants in the prevention and treatment of oxidative stress-related conditions is continuously increasing and many efforts have been targeted on the synthesis of new antioxidants with low cytotoxicity (24)(25)(26).…”

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confidence: 99%

Synthesis, in vitro safety and antioxidant activity of new pyrrole hydrazones

et al. 2020

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Six new N-pyrrolylhydrazide hydrazones were synthesized under micro synthesis conditions, assuring about 59–93 % yield, low harmful emissions and reagent economy. The structures of the new compounds were elucidated by melting points, TLC characteristics, IR, 1H and 13C NMR spectral data followed by MS data. The purity of the obtained compounds was proven by the corresponding elemental analyses. “Lipinski’s rule of five” parameters were applied for preliminary evaluation of the pharmacokinetic properties of the target molecules. The initial in vitro safety screening for cytotoxicity (on HepG2 cells) and hemocompatibility (hemolysis assay) showed good safety of the new compounds, where ethyl 5-(4-bromophenyl)-1-(1-(2-(4-hydroxy-3-methoxybenzylidene)-hydrazineyl)-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyr-role-3-carboxylate (4d) and ethyl 5-(4-bromophenyl)-1-(1-(2-(2-hydroxybenzylidene)hydrazineyl)-1-oxo-3-phenylpropan--2-yl)-2-methyl-1H-pyrrole-3-carboxylate (4a) were the least toxic. The antioxidant activity in terms of radical scavenging activity (DPPH test) and reducing ability (ABTS) was also evaluated. The antioxidant protective potential of the compounds was next determined in different in vitro cellular-based models, revealing compounds 4d and 3 [ethyl 5-(4-bromophenyl)-1-(1-hydrazineyl-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate] as the most promising compounds, with 4d having better safety profile.

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“…The marker of DNA damage is 8-oxoguanine, a chemical derivative of guanine [53,54]. Oxidative stress is associated with many diseases, including epidemiologically significant diseases of affluence such as cancer [55], cardiovascular disease [56], obesity [57], neurodegenerative diseases [58] and allergic diseases [59]. Oxygen metabolism and the prevalence of ROS have forced living organisms to develop appropriate counteraction mechanisms to minimize the negative effects of oxidative stress [60].…”

Section: Ionizing Radiation As a Source Of Reactive Oxygen Speciesmentioning

confidence: 99%

Ionizing Radiation as a Source of Oxidative Stress—The Protective Role of Melatonin and Vitamin D

Nuszkiewicz

Woźniak

Szewczyk-Golec

2020

IJMS

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Ionizing radiation (IR) has found widespread application in modern medicine, including medical imaging and radiotherapy. As a result, both patients and healthcare professionals are exposed to various IR doses. To minimize the negative side effects of radiation associated with oxidative imbalance, antioxidant therapy has been considered. In this review, studies on the effects of melatonin and vitamin D on radiation-induced oxidative stress are discussed. According to the research data, both substances meet the conditions for use as agents that protect humans against IR-induced tissue damage. Numerous studies have confirmed that melatonin, a hydro- and lipophilic hormone with strong antioxidant properties, can potentially be used as a radioprotectant in humans. Less is known about the radioprotective effects of vitamin D, but the results to date have been promising. Deficiencies in melatonin and vitamin D are common in modern societies and may contribute to the severity of adverse side effects of medical IR exposure. Hence, supporting supplementation with both substances seems to be of first importance. Interestingly, both melatonin and vitamin D have been found to selectively radiosensitise cancer cells, which makes them promising adjuvants in radiotherapy. More research is needed in this area, especially in humans.

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The Underlying Role of Oxidative Stress in Neurodegeneration: A Mechanistic Review

Cited by 133 publications

References 0 publications

Melatonin and inflammation—Story of a double‐edged blade

Melatonin and inflammation—Story of a double‐edged blade

Synthesis, in vitro safety and antioxidant activity of new pyrrole hydrazones

Ionizing Radiation as a Source of Oxidative Stress—The Protective Role of Melatonin and Vitamin D

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