The Epigenetic Reader Methyl-CpG-Binding Protein 2 (MeCP2) Is an Emerging Oncogene in Cancer Biology

Cancers, Journal Year: 2023, Volume and Issue: 15(10), P. 2683 - 2683

Published: May 9, 2023

Epigenetic mechanisms are gene regulatory processes that control expression and cellular identity. factors include the "writers", "readers", "erasers" of epigenetic modifications such as DNA methylation. Accordingly, nuclear protein Methyl-CpG-Binding Protein 2 (MeCP2) is a reader methylation with key roles in identity function. Research studies have linked altered methylation, deregulation MeCP2 levels, or

Language: Английский

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Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 457 - 457

Published: Feb. 18, 2024

Multiple lines of evidence have shown that lactate-mediated pH alterations in the brains patients with neuropsychiatric diseases such as schizophrenia (SCZ), Alzheimer’s disease (AD) and autism may be attributed to mitochondrial dysfunction changes energy metabolism. While neuronal activity is associated reduction brain pH, astrocytes are responsible for rebalancing maintain equilibrium. As lactate level main determinant activities impacted by due binding protons (H+) various types proteins, altering their structure function non-neuronal cells brain. Lactate could affect diverse epigenetic modifications, including histone lactylation, which linked acetylation DNA methylation. In this review, we discuss importance homeostasis normal function, role an essential regulatory molecule its contributions abnormalities diseases, shed light on lactate-based pH-modulating therapies targeting modifications. conclusion, attempt highlight potentials challenges translating lactate-pH-modulating clinics treatment diseases.

Language: Английский

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Emerging roles of epigenetics in lead-induced neurotoxicity

Environment International, Journal Year: 2023, Volume and Issue: 181, P. 108253 - 108253

Published: Oct. 13, 2023

Lead is a common environmental heavy metal contaminant. Humans are highly susceptible to lead accumulation in the body, which causes nervous system damage and leads variety of diseases, such as Alzheimer's disease, Parkinson's autism spectrum disorder. Recent research has focused on mechanisms lead-induced neurotoxicity at multiple levels, including DNA methylation, histone modifications, non-coding RNAs, involved various diseases. We reviewed latest articles summarised emerging roles modification, RNAs neurotoxicity. Our summary provides theoretical basis directions for future prevention, diagnosis, treatment neurological

Language: Английский

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Neurotrophins and Their Receptors: BDNF’s Role in GABAergic Neurodevelopment and Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8312 - 8312

Published: July 30, 2024

Neurotrophins and their receptors are distinctly expressed during brain development play crucial roles in the formation, survival, function of neurons nervous system. Among these molecules, brain-derived neurotrophic factor (BDNF) has garnered significant attention due to its involvement regulating GABAergic system function. In this review, we summarize compare expression patterns neurotrophins both developing adult brains rodents, macaques, humans. Then, focus on implications BDNF from cortex striatum, as presence single nucleotide polymorphisms disruptions levels alter excitatory/inhibitory balance brain. This imbalance different pathogenesis neurodevelopmental diseases like autism spectrum disorder (ASD), Rett syndrome (RTT), schizophrenia (SCZ). Altogether, evidence shows that neurotrophins, especially BDNF, essential for development, maintenance, brain, or signaling common mechanisms pathophysiology diseases.

Language: Английский

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Mitochondrial metabolism and neuroinflammation in the cerebral cortex and cortical synapses of rats: effect of milk intake through DNA methylation

The Journal of Nutritional Biochemistry, Journal Year: 2024, Volume and Issue: 128, P. 109624 - 109624

Published: March 20, 2024

Brain plasticity and cognitive functions are tightly influenced by foods or nutrients, which determine a metabolic modulation having long-term effect on health, involving also epigenetic mechanisms. Breast milk formula based cow is the first food for human beings, who, throughout their lives, then exposed to different types of milk. We previously demonstrated that rats fed with derived from distinct species, compositions nutritional properties, display selective systemic inflammatory profiles through changes mitochondrial redox state in liver, skeletal cardiac muscle. Here, rat model, we isoenergetic supplementation (CM), donkey (DM) (HM) impacts brain cortex cortical synapses, affecting neuroinflammation synaptic plasticity. Interestingly, found administration modulates DNA methylation consequently affects gene expression. Our results emphasize importance nutrition synapse physiology, highlight key role played this context mitochondria, nutrient-sensitive organelles able orchestrate responses.

Language: Английский

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BDNF Modulation by microRNAs: An Update on the Experimental Evidence

Cells, Journal Year: 2024, Volume and Issue: 13(10), P. 880 - 880

Published: May 20, 2024

MicroRNAs can interfere with protein function by suppressing their messenger RNA translation or the synthesis of its related factors. The brain-derived neurotrophic factor (BDNF) is essential to proper formation and nervous system seen be regulated many microRNAs. However, understanding how microRNAs influence BDNF actions within cells requires a wider comprehension integrative regulatory mechanisms.

Language: Английский

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The Potential Therapeutic Application of Simvastatin for Brain Complications and Mechanisms of Action

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(7), P. 914 - 914

Published: June 22, 2023

Statins are common drugs that clinically used to reduce elevated plasma cholesterol levels. Based on their solubility, statins considered be either hydrophilic or lipophilic. Amongst them, simvastatin has the highest lipophilicity facilitate its ability cross blood-brain barrier. Recent studies have suggested could a promising therapeutic option for different brain complications and diseases ranging from tumors (i.e., medulloblastoma glioblastoma) neurological disorders Alzheimer's disease, Parkinson's Huntington's disease). Specific mechanisms of disease amelioration, however, still unclear. Independent suggest may risk developing certain neurodegenerative disorders. Meanwhile, other point towards inducing cell death in tumor lines. In this review, we outline potential effects review relevant molecular cases.

Language: Английский

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NEAT1-mediated regulation of proteostasis and mRNA localization impacts autophagy dysregulation in Rett syndrome

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(4)

Published: Jan. 28, 2025

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by loss-of-function mutations in the MECP2 gene, resulting diverse cellular dysfunctions. Here, we investigated role of long noncoding RNA (lncRNA) NEAT1 context MeCP2 deficiency using human neural cells and RTT patient samples. Through single-cell sequencing molecular analyses, found that markedly downregulated knockout (KO) at various stages differentiation. downregulation correlated with aberrant activation mTOR pathway, abnormal protein metabolism, dysregulated autophagy, contributing to accumulation aggregates impaired mitochondrial function. Reactivation MECP2-KO rescued these phenotypes, indicating its critical downstream MECP2. Furthermore, direct RNA-RNA interaction was revealed as key process for influence on autophagy genes, leading altered subcellular localization specific autophagy-related messenger RNAs biogenesis autophagic complexes. Importantly, restoration morphological defects observed neurons, highlighting crucial neuronal maturation. Overall, our findings elucidate lncRNA mediator function, regulating essential pathways involved morphology.

Language: Английский

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Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Nov. 29, 2024

DNA methylation plays a crucial role in development, aging, degeneration of various tissues and dedifferentiated cells. This review explores the multifaceted impact on retina brain during development pathological processes. First, we investigate retinal then focus diseases, detailing changes patterns diseases such as diabetic retinopathy (DR), age-related macular (AMD), glaucoma. Since is considered an extension brain, its unique structure allows it to exhibit similar immune response mechanisms brain. We further extend our exploration from examining associated Alzheimer's disease (AD) Huntington's (HD) better understand mechanistic links between explore possibility communication visual system central nervous (CNS) epigenetic perspective. Additionally, discuss neurodevelopmental including schizophrenia (SZ), autism spectrum disorder (ASD), intellectual disability (ID), how affects neuronal synaptic plasticity, cognitive function, providing insights into molecular underlying disorders.

Language: Английский

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MeCP2 ubiquitination and sumoylation, in search of a function

Human Molecular Genetics, Journal Year: 2023, Volume and Issue: 33(1), P. 1 - 11

Published: Sept. 11, 2023

Abstract MeCP2 (Methyl CpG binding protein 2) is an intrinsically disordered that binds to methylated genome regions. The a critical transcriptional regulator of the brain, and its mutations account for 95% Rett syndrome (RTT) cases. Early studies this neurodevelopmental disorder revealed close connection with dysregulations ubiquitin system (UbS), notably as related UBE3A, ligase involved in proteasome-mediated degradation proteins. undergoes numerous post-translational modifications (PTMs), including ubiquitination sumoylation, which, addition potential functional outcomes their monomeric forms gene regulation synaptic plasticity, polymeric organization, these play role proteasomal degradation. UbS-mediated crucial maintaining homeostasis proper function decreasing some RTT-causing mutations. However, regardless all connections UbS, molecular details signaling targeting by ubiquitin-proteasome (UPS) roles sumoylation remain largely unexplored are focus review.

Language: Английский

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