Histone acetylation in neuronal (dys)function

2016 ◽  
Vol 7 (2) ◽  
pp. 103-116 ◽  
Author(s):  
Emilie M. Bonnaud ◽  
Elsa Suberbielle ◽  
Cécile E. Malnou
Keyword(s):  
Gene Expression ◽  
Histone Acetylation ◽  
Cognitive Functions ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Infectious Agents ◽  
Pathological Conditions ◽  
Neuronal Gene ◽  
Environmental Causes ◽  
Neuronal Functions

AbstractCognitive functions require the expression of an appropriate pattern of genes in response to environmental stimuli. Over the last years, many studies have accumulated knowledge towards the understanding of molecular mechanisms that regulate neuronal gene expression. Epigenetic modifications have been shown to play an important role in numerous neuronal functions, from synaptic plasticity to learning and memory. In particular, histone acetylation is a central player in these processes. In this review, we present the molecular mechanisms of histone acetylation and summarize the data underlying the relevance of histone acetylation in cognitive functions in normal and pathological conditions. In the last part, we discuss the different mechanisms underlying the dysregulation of histone acetylation associated with neurological disorders, with a particular focus on environmental causes (stress, drugs, or infectious agents) that are linked to impaired histone acetylation.

scholarly journals The Anti-Neuroinflammatory Role of Anthocyanins and Their Metabolites for the Prevention and Treatment of Brain Disorders

2020 ◽  
Vol 21 (22) ◽  
pp. 8653
Author(s):  
Joana F. Henriques ◽  
Diana Serra ◽  
Teresa C. P. Dinis ◽  
Leonor M. Almeida
Keyword(s):  
Neurological Disorders ◽  
Fruits And Vegetables ◽  
Molecular Mechanisms ◽  
Brain Inflammation ◽  
Brain Diseases ◽  
Naturally Occurring ◽  
Pathological Conditions ◽  
Promising Strategy ◽  
Prevention And Treatment

Anthocyanins are naturally occurring polyphenols commonly found in fruits and vegetables. Numerous studies have described that anthocyanin-rich foods may play a crucial role in the prevention and treatment of different pathological conditions, which have encouraged their consumption around the world. Anthocyanins exhibit a significant neuroprotective role, mainly due to their well-recognized antioxidant and anti-inflammatory properties. Neuroinflammation is an intricate process relevant in both homeostatic and pathological circumstances. Since the progression of several neurological disorders relies on neuroinflammatory process, targeting brain inflammation has been considered a promising strategy in those conditions. Recent data have shown the anti-neuroinflammatory abilities of many anthocyanins and of their metabolites in the onset and development of several neurological disorders. In this review, it will be discussed the importance and the applicability of these polyphenolic compounds as neuroprotective agents and it will be also scrutinized the molecular mechanisms underlying the modulation of neuroinflammation by these natural compounds in the context of several brain diseases.

scholarly journals The Study of Cerebrospinal Fluid microRNAs in Spinal Cord Injury and Neurodegenerative Diseases: Methodological Problems and Possible Solutions

2021 ◽  
Vol 23 (1) ◽  
pp. 114
Author(s):  
Irina Baichurina ◽  
Victor Valiullin ◽  
Victoria James ◽  
Albert Rizvanov ◽  
Yana Mukhamedshina
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Rna Isolation ◽  
Cord Injury

Despite extensive research on neurological disorders, unanswered questions remain regarding the molecular mechanisms underpinning the course of these diseases, and the search continues for effective biomarkers for early diagnosis, prognosis, or therapeutic intervention. These questions are especially acute in the study of spinal cord injury (SCI) and neurodegenerative diseases. It is believed that the changes in gene expression associated with processes triggered by neurological disorders are the result of post-transcriptional gene regulation. microRNAs (miRNAs) are key regulators of post-transcriptional gene expression and, as such, are often looked to in the search for effective biomarkers. We propose that cerebrospinal fluid (CSF) is potentially a source of biomarkers since it is in direct contact with the central nervous system and therefore may contain biomarkers indicating neurodegeneration or damage to the brain and spinal cord. However, since the abundance of miRNAs in CSF is low, their isolation and detection is technically difficult. In this review, we evaluate the findings of recent studies of CSF miRNAs as biomarkers of spinal cord injury (SCI) and neurodegenerative diseases. We also summarize the current knowledge concerning the methods of studying miRNA in CSF, including RNA isolation and normalization of the data, highlighting the caveats of these approaches and possible solutions.

scholarly journals Inhibition of HIF-prolyl 4-hydroxylases as a promising approach to the therapy of cardiometabolic diseases

2018 ◽  
Vol 90 (8) ◽  
pp. 86-94
Author(s):  
K A Aitbaev ◽  
I T Murkamilov ◽  
V V Fomin
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Innate Immune ◽  
Anaerobic Glycolysis ◽  
Cardiometabolic Diseases ◽  
Hypoxic Conditions ◽  
Pathological Conditions

Prolyl-4-hydroxylases of hypoxia-inducible factor (HIF-P4Hs) are enzymes that, under the conditions of normoxia, cause degradation of the HIF-transcriptional protein, which regulates a number of metabolic processes, including erythropoiesis, glucose level and lipid metabolism. In hypoxic conditions, on the contrary, their activity is suppressed and HIF stabilization takes place. This mechanism, i.e. stabilization of HIF by inhibition of HIF-P4Hs was the basis for the development of drugs designed for treatment of renal anemia, which are currently in stages 2 and 3 of clinical trials and are showing encouraging results. Recently, it has also been reported that inhibition of HIF-P4Hs can be effective in treatment of cardiometabolic diseases - coronary heart disease, hypertension, obesity, metabolic syndrome, diabetic cardiomyopathy and atherosclerosis. The review, based on the most recent data, discusses in detail molecular mechanisms of therapeutic effect of HIF-P4Hs inhibition in these pathological conditions and provides evidence that these mechanisms are associated with HIF stabilization and gene expression, improving perfusion and endothelial function, reprogramming metabolism from oxidative phosphorylation to anaerobic glycolysis, reducing inflammation and having beneficial effect on the innate immune system.

The Mechanisms Behind the Biological Activity of Flavonoids

2019 ◽  
Vol 26 (39) ◽  
pp. 6976-6990 ◽  
Author(s):  
Ana María González-Paramás ◽  
Begoña Ayuda-Durán ◽  
Sofía Martínez ◽  
Susana González-Manzano ◽  
Celestino Santos-Buelga
Keyword(s):  
Gene Expression ◽  
Biological Activity ◽  
Phenolic Compounds ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Radical Scavenging ◽  
Model Organism ◽  
Stress Theory ◽  
Radical Scavenging Properties

: Flavonoids are phenolic compounds widely distributed in the human diet. Their intake has been associated with a decreased risk of different diseases such as cancer, immune dysfunction or coronary heart disease. However, the knowledge about the mechanisms behind their in vivo activity is limited and still under discussion. For years, their bioactivity was associated with the direct antioxidant and radical scavenging properties of phenolic compounds, but nowadays this assumption is unlikely to explain their putative health effects, or at least to be the only explanation for them. New hypotheses about possible mechanisms have been postulated, including the influence of the interaction of polyphenols and gut microbiota and also the possibility that flavonoids or their metabolites could modify gene expression or act as potential modulators of intracellular signaling cascades. This paper reviews all these topics, from the classical view as antioxidants in the context of the Oxidative Stress theory to the most recent tendencies related with the modulation of redox signaling pathways, modification of gene expression or interactions with the intestinal microbiota. The use of C. elegans as a model organism for the study of the molecular mechanisms involved in biological activity of flavonoids is also discussed.

scholarly journals The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

2020 ◽  
Vol 31 (4) ◽  
pp. 716-730 ◽  
Author(s):  
Marc Johnsen ◽  
Torsten Kubacki ◽  
Assa Yeroslaviz ◽  
Martin Richard Späth ◽  
Jannis Mörsdorf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Caloric Restriction ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hypoxic Preconditioning ◽  
Preventive Strategies ◽  
Gene Expression Signatures

BackgroundAlthough AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance.MethodsTo identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury.ResultsThe gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI.ConclusionsThis comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

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