scholarly journals Secondary Metabolites with Antioxidant Activities for the Putative Treatment of Amyotrophic Lateral Sclerosis (ALS): “Experimental Evidences”

2020 ◽  
Vol 2020 ◽  
pp. 1-22
Author(s):  
Jamire M. Silva ◽  
Michelangela S. C. Nobre ◽  
Sonaly L. Albino ◽  
Lucas L. Lócio ◽  
Agnis P. S. Nascimento ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Therapeutic Potential ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
New Drugs ◽  
Alternative Form ◽  
Antioxidant Compounds ◽  
Nitrogenous Compounds ◽  
Age Related ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that is characterized by progressive loss of the upper and lower motor neurons at the spinal or bulbar level. Oxidative stress (OS) associated with mitochondrial dysfunction and the deterioration of the electron transport chain are factors that contribute to neurodegeneration and perform a potential role in the pathogenesis of ALS. Natural antioxidant molecules have been proposed as an alternative form of treatment for the prevention of age-related neurological diseases, in which ALS is included. Researches support that regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in this disease, and antioxidant drugs are aimed at a promising pathway to treatment. Among the strategies used for obtaining new drugs, we can highlight the isolation of secondary metabolite compounds from natural sources that, along with semisynthetic derivatives, correspond to approximately 40% of the drugs found on the market. Among these compounds, we emphasize oxygenated and nitrogenous compounds, such as flavonoids, coumarins, and alkaloids, in addition to the fatty acids, that already stand out in the literature for their antioxidant properties, consisting in a part of the diets of millions of people worldwide. Therefore, this review is aimed at presenting and summarizing the main articles published within the last years, which represent the therapeutic potential of antioxidant compounds of natural origin for the treatment of ALS.

Structurally Related Edaravone Analogues: Synthesis, Antiradical, Antioxidant, and Copper-Chelating Properties

2020 ◽  
Vol 18 (10) ◽  
pp. 779-790 ◽  
Author(s):  
Alexandre LeBlanc ◽  
Miroslava Cuperlovic-Culf ◽  
Pier Jr. Morin ◽  
Mohamed Touaibia
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Therapeutic Options ◽  
Partial Charge ◽  
Associated Diseases ◽  
Significant Interest ◽  
Lateral Sclerosis

Background:: The current therapeutic options available to patients diagnosed with Amyotrophic Lateral Sclerosis (ALS) are limited and edaravone is a compound that has gained significant interest for its therapeutic potential in this condition. Objectives: : The current work was thus undertaken to synthesize and characterize a series of edaravone analogues. Methods: A total of 17 analogues were synthesized and characterized for their antioxidant properties, radical scavenging potential and copper-chelating capabilities. Results: Radical scavenging and copper-chelating properties were notably observed for edaravone. Analogues bearing hydrogen in position 1 and a phenyl at position 3 and a phenyl in both positions of pyrazol-5 (4H)-one displayed substantial radical scavenging, antioxidants and copper-chelating properties. High accessibility of electronegative groups combined with higher electronegativity and partial charge of the carbonyl moiety in edaravone might explain the observed difference in the activity of edaravone relative to the closely related analogues 6 and 7 bearing hydrogen at position 1 and a phenyl at position 3 (6) and a phenyl in both positions (7). Conclusion: Overall, this study reveals a subset of edaravone analogues with interesting properties. Further investigation of these compounds is foreseen in relevant models of oxidative stress-associated diseases in order to assess their therapeutic potential in such conditions.

Antioxidant properties of lingonberry (Vaccinium vitis-idaea L.) leaves within a set of wild clones and cultivars

2015 ◽  
Vol 95 (4) ◽  
pp. 663-669 ◽  
Author(s):  
Poorva Vyas ◽  
Nicholas H. Curran ◽  
Abir U. Igamberdiev ◽  
Samir C. Debnath
Keyword(s):  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Antioxidant Compounds ◽  
Soluble Phenolics ◽  
Reduced Temperature

Vyas, P., Curran, N. H., Igamberdiev, A. U. and Debnath, S. C. 2015. Antioxidant properties of lingonberry (Vaccinium vitis-idaea L.) leaves within a set of wild clones and cultivars. Can. J. Plant Sci. 95: 663–669. The antioxidant activities and the contents of total soluble phenolics, flavonoids, anthocyanins and proanthocyanidins were studied in wild and cultivated lingonberries (Vaccinium vitis-idaea L.). The antioxidant properties of wild clones were much higher than those of the cultivars. The levels of antioxidant compounds were positively correlated with latitude, altitude, reduced temperature and increased precipitation of the collected sites.

Proteinase inhibition and antioxidant activity of selected forage crops

Biologia ◽  
2011 ◽  
Vol 66 (1) ◽  
Author(s):  
Tibor Maliar ◽  
Jarmila Drobná ◽  
Ján Kraic ◽  
Mária Maliarová ◽  
Jana Jurovatá
Keyword(s):  
Antioxidant Activity ◽  
Trifolium Pratense ◽  
Therapeutic Potential ◽  
Antioxidant Activities ◽  
Local Population ◽  
Antioxidant Properties ◽  
Inhibition Activity ◽  
Forage Crops ◽  
Starting Point ◽  
Proteinase Inhibition

AbstractThe hypothesis of the possible therapeutic potential of selected species of forage crops is discussed. Extracts from genotypes of Anthyllis sp., Astragalus sp., Coronilla sp., Lotus sp., Medicago sp., Melilotus sp., Onobrychis sp. and Trifolium sp. were prepared and tested for proteinase inhibition and antioxidant activities. We found that Trifolium pratense accession POLKIE99-3 expressed the highest relative trypsin inhibition activity (80.0%) compared to standards. The highest thrombin inhibition activity (81.4%) was detected in the Medicago sativa old cultivar Hodoninka, whereas the highest relative urokinase inhibition activity (62.5%) was expressed by the local population Nitranka. Relatively high antioxidant properties of Trifolium sp. accessions, Trifolium pratense genetic resources SVKZAH98-40, were of interest. Results of this study confirmed that there are significant differences in proteinase inhibition and antioxidant activity among important selected agricultural crops. The present paper may also be the starting point of the research aimed for development of new functional food and nutraceuticals, and/or of the research focused on new secondary metabolites with potential as bioactive compounds.

scholarly journals d-amino Acids in Health and Disease: A Focus on Cancer

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2205 ◽  
Author(s):  
Jacco J.A.J. Bastings ◽  
Hans M. van Eijk ◽  
Steven W. Olde Damink ◽  
Sander S. Rensen
Keyword(s):  
Amino Acids ◽  
Human Physiology ◽  
Amyotrophic Lateral Sclerosis ◽  
Human Body ◽  
Physiological Processes ◽  
Gut Barrier Function ◽  
Age Related ◽  
Health And Disease ◽  
Living Organisms ◽  
Lateral Sclerosis

d-amino acids, the enantiomeric counterparts of l-amino acids, were long considered to be non-functional or not even present in living organisms. Nowadays, d-amino acids are acknowledged to play important roles in numerous physiological processes in the human body. The most commonly studied link between d-amino acids and human physiology concerns the contribution of d-serine and d-aspartate to neurotransmission. These d-amino acids and several others have also been implicated in regulating innate immunity and gut barrier function. Importantly, the presence of certain d-amino acids in the human body has been linked to several diseases including schizophrenia, amyotrophic lateral sclerosis, and age-related disorders such as cataract and atherosclerosis. Furthermore, increasing evidence supports a role for d-amino acids in the development, pathophysiology, and treatment of cancer. In this review, we aim to provide an overview of the various sources of d-amino acids, their metabolism, as well as their contribution to physiological processes and diseases in man, with a focus on cancer.

scholarly journals The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis

2017 ◽  
Vol 9 (391) ◽  
pp. eaaf3962 ◽  
Author(s):  
Keiko Imamura ◽  
Yuishin Izumi ◽  
Akira Watanabe ◽  
Kayoko Tsukita ◽  
Knut Woltjen ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neurons ◽  
New Drugs ◽  
Small Interfering Rnas ◽  
Altered Expression ◽  
Sporadic Als ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1). Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway. Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro. Knockdown of Src or c-Abl with small interfering RNAs (siRNAs) also rescued ALS motor neuron degeneration. One of the hits, bosutinib, boosted autophagy, reduced the amount of misfolded mutant SOD1 protein, and attenuated altered expression of mitochondrial genes. Bosutinib also increased survival in vitro of ALS iPSC-derived motor neurons from patients with sporadic ALS or other forms of familial ALS caused by mutations in TAR DNA binding protein (TDP-43) or repeat expansions in C9orf72. Furthermore, bosutinib treatment modestly extended survival of a mouse model of ALS with an SOD1 mutation, suggesting that Src/c-Abl may be a potentially useful target for developing new drugs to treat ALS.

scholarly journals Amyotrophic lateral sclerosis: pathogenetic mechanisms and new approaches to pharmacotherapy (literature review)

2019 ◽  
Vol 8 (4) ◽  
pp. 12-18
Author(s):  
T. M. Alekseeva ◽  
T. R. Stuchevskaya ◽  
V. S. Demeshonok
Keyword(s):  
Clinical Trials ◽  
Amyotrophic Lateral Sclerosis ◽  
New Drugs ◽  
Significant Progress ◽  
Future Directions ◽  
Loss Of Self ◽  
The World ◽  
Self Service ◽  
Lateral Sclerosis ◽  
Made In

Amyotrophic lateral sclerosis is a neurodegenerative disease, resulting in the loss of self-service and death of the middle-aged and elderly people. In the last 2 decades, significant progress has been made in the study of the pathogenesis of this disease. Two known drugs (riluzole and edaravone) have been approved by the Food and Drug Administration for treatment of amyotrophic lateral sclerosis. The efficacy of these drugs is extremely low, so clinical trials of new drugs are ongoing all over the world. This review discusses the current achievements and future directions of therapy of this disease.

scholarly journals Therapeutic Potential of Polyphenols in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1328
Author(s):  
Valentina Novak ◽  
Boris Rogelj ◽  
Vera Župunski
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Frontotemporal Dementia ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Common Disease ◽  
Beneficial Effects ◽  
Disease Spectrum ◽  
New Compounds ◽  
And Oxidative Stress ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are severe neurodegenerative disorders that belong to a common disease spectrum. The molecular and cellular aetiology of the spectrum is a highly complex encompassing dysfunction in many processes, including mitochondrial dysfunction and oxidative stress. There is a paucity of treatment options aside from therapies with subtle effects on the post diagnostic lifespan and symptom management. This presents great interest and necessity for the discovery and development of new compounds and therapies with beneficial effects on the disease. Polyphenols are secondary metabolites found in plant-based foods and are well known for their antioxidant activity. Recent research suggests that they also have a diverse array of neuroprotective functions that could lead to better treatments for neurodegenerative diseases. We present an overview of the effects of various polyphenols in cell line and animal models of ALS/FTD. Furthermore, possible mechanisms behind actions of the most researched compounds (resveratrol, curcumin and green tea catechins) are discussed.

scholarly journals Conserved metabolite regulation of stress granule assembly via AdoMet

2020 ◽  
Vol 219 (8) ◽  
Author(s):  
Kyle Begovich ◽  
Anthony Q. Vu ◽  
Gene Yeo ◽  
James E. Wilhelm
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Metabolic Activity ◽  
Therapeutic Potential ◽  
Growth Stress ◽  
Evolutionarily Conserved ◽  
Acute Elevation ◽  
Metabolic Stresses ◽  
Lateral Sclerosis ◽  
Metabolite Regulation

Stress granules (SGs) are evolutionarily conserved condensates of ribonucleoproteins that assemble in response to metabolic stresses. Because aberrant SG formation is associated with amyotrophic lateral sclerosis (ALS), understanding the connection between metabolic activity and SG composition can provide therapeutic insights into neurodegeneration. Here, we identify 17 metabolic enzymes recruited to yeast SGs in response to physiological growth stress. Furthermore, the product of one of these enzymes, AdoMet, is a regulator of SG assembly and composition. Decreases in AdoMet levels increase SG formation, while chronic elevation of AdoMet produces SG remnants lacking proteins associated with the 5′ end of transcripts. Interestingly, acute elevation of AdoMet blocks SG formation in yeast and motor neurons. Treatment of ALS-derived motor neurons with AdoMet also suppresses the formation of TDP-43–positive SGs, a hallmark of ALS. Together, these results argue that AdoMet is an evolutionarily conserved regulator of SG composition and assembly with therapeutic potential in neurodegeneration.

scholarly journals Oxidative Stress in Amyotrophic Lateral Sclerosis: Pathophysiology and Opportunities for Pharmacological Intervention

2020 ◽  
Vol 2020 ◽  
pp. 1-29
Author(s):  
Teresa Cunha-Oliveira ◽  
Liliana Montezinho ◽  
Catarina Mendes ◽  
Omidreza Firuzi ◽  
Luciano Saso ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Therapeutic Benefit ◽  
Pharmacological Intervention ◽  
Antioxidant Compounds ◽  
Pathological Feature ◽  
Beneficial Effects ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease or Charcot disease, is a fatal neurodegenerative disease that affects motor neurons (MNs) and leads to death within 2–5 years of diagnosis, without any effective therapy available. Although the pathological mechanisms leading to ALS are still unknown, a wealth of evidence indicates that an excessive reactive oxygen species (ROS) production associated with an inefficient antioxidant defense represents an important pathological feature in ALS. Substantial evidence indicates that oxidative stress (OS) is implicated in the loss of MNs and in mitochondrial dysfunction, contributing decisively to neurodegeneration in ALS. Although the modulation of OS represents a promising approach to protect MNs from degeneration, the fact that several antioxidants with beneficial effects in animal models failed to show any therapeutic benefit in patients raises several questions that should be analyzed. Using specific queries for literature search on PubMed, we review here the role of OS-related mechanisms in ALS, including the involvement of altered mitochondrial function with repercussions in neurodegeneration. We also describe antioxidant compounds that have been mostly tested in preclinical and clinical trials of ALS, also describing their respective mechanisms of action. While the description of OS mechanism in the different mutations identified in ALS has as principal objective to clarify the contribution of OS in ALS, the description of positive and negative outcomes for each antioxidant is aimed at paving the way for novel opportunities for intervention. In conclusion, although antioxidant strategies represent a very promising approach to slow the progression of the disease, it is of utmost need to invest on the characterization of OS profiles representative of each subtype of patient, in order to develop personalized therapies, allowing to understand the characteristics of antioxidants that have beneficial effects on different subtypes of patients.

Sign in / Sign up

Export Citation Format

Share Document