Neuroprotective effects of novel nitrones: In vitro and in silico studies.

Neuroprotective effects of novel nitrones: In vitro and in silico studies. Eur J Pharmacol. 2020 Jan 17;:172926 Authors: Cancela S, Canclini L, Mourglia-Ettlin G, Hernández P, Merlino A Abstract Neurodegenerative diseases affect millions of people around the world. Several studies point out caspase-3 as a key player in the development and progression of neurological disorders including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's and Huntington's diseases. Furthermore, oxidative stress and mitochondrial dysfunction plays an important role in neurodegenerative pathologies leading to neuronal damage and cell death. Pharmacological properties of nitrones such as free radical trapping and neuroprotection has been previously described. In the present work, we have assessed ten non-cytotoxic nitrones for their ability to inhibit apoptosis plus their potential to reduce active caspase-3 and oxidative stress in the hippocampal neuronal cell line HT22. Our results highlight the faculty of nitrones to inhibit apoptosis by a mechanism that involves active caspase-3 reduction and decrease of reactive oxygen species. Moreover, docking and molecular dynamics approaches lead to a detailed analysis at the atomic level of the nitrones binding mode to caspase-3 suggesting that compounds bind in a region close to the catalytic site. All these data place these molecules as excellent hits for further efforts to redesign novel compounds in the search of a ne...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research

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Abstract The global burden of neurodegenerative diseases is alarmingly increasing in parallel to the aging of population. Although the molecular mechanisms leading to neurodegeneration are not completely understood, excitotoxicity, defined as to the injury and death of neurons due to an excessive or prolonged exposure to excitatory amino acids, has been shown to play a pivotal role. The increased release and/or decreased uptake of glutamate results in a dysregulation of neuronal calcium homeostasis, leading to oxidative stress, mitochondrial dysfunctions, disturbances in protein turn-over and neuroinflammation. De...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
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Source: International Journal of Medical Sciences - Category: Biomedical Science Tags: Int J Med Sci Source Type: research
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Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research
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Source: Cell Metabolism - Category: Cytology Authors: Tags: Cell Metab Source Type: research
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Source: Mitochondrion - Category: Biochemistry Source Type: research
Conclusion The key problem with the ND field is the lack of understanding in the events preceding the development of protein-based markers – such as Tau – currently used to diagnose NDs. By this stage, the diseases become more difficult to treat. SncRNAs play an important regulatory role in the maintenance of the homeostatic brain. Therefore, changes in their concentration levels can be indicative of mechanistic changes that could precede protein-based markers. One single sncRNA biomarker is unlikely to differentiate between diseases. However, a combination of sncRNA biomarkers could be illustrative of the me...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
Conclusions In this review, we analyzed mechanisms through which mitobolites, a distinct set of mitochondria-generated metabolites, can be released from mitochondria and then act as second messengers that contribute to cellular and organismal aging by regulating longevity-defining processes outside of mitochondria. Our analysis indicates that in eukaryotes across phyla, these second messengers of cellular aging exhibit the following common features: (1) they are produced in mitochondria in response to certain changes in the nutrient, stress, proliferation or age status of the cell; it remains unknown, however, what kind o...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
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