scholarly journals Epigenetic Effects Induced by Methamphetamine and Methamphetamine-Dependent Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-28 ◽  
Author(s):  
Fiona Limanaqi ◽  
Stefano Gambardella ◽  
Francesca Biagioni ◽  
Carla L. Busceti ◽  
Francesco Fornai
Keyword(s):  
Molecular Mechanisms ◽  
Neuropsychiatric Disorders ◽  
Behavioral Alterations ◽  
Neuronal Phenotype ◽  
Cellular Events ◽  
Epigenetic Effects ◽  
Molecular Events ◽  
Epigenetic Events ◽  
Genetic Modifications ◽  
Altered Gene

Methamphetamine is a widely abused drug, which possesses neurotoxic activity and powerful addictive effects. Understanding methamphetamine toxicity is key beyond the field of drug abuse since it allows getting an insight into the molecular mechanisms which operate in a variety of neuropsychiatric disorders. In fact, key alterations produced by methamphetamine involve dopamine neurotransmission in a way, which is reminiscent of spontaneous neurodegeneration and psychiatric schizophrenia. Thus, understanding the molecular mechanisms operated by methamphetamine represents a wide window to understand both the addicted brain and a variety of neuropsychiatric disorders. This overlapping, which is already present when looking at the molecular and cellular events promoted immediately after methamphetamine intake, becomes impressive when plastic changes induced in the brain of methamphetamine-addicted patients are considered. Thus, the present manuscript is an attempt to encompass all the molecular events starting at the presynaptic dopamine terminals to reach the nucleus of postsynaptic neurons to explain how specific neurotransmitters and signaling cascades produce persistent genetic modifications, which shift neuronal phenotype and induce behavioral alterations. A special emphasis is posed on disclosing those early and delayed molecular events, which translate an altered neurotransmitter function into epigenetic events, which are derived from the translation of postsynaptic noncanonical signaling into altered gene regulation. All epigenetic effects are considered in light of their persistent changes induced in the postsynaptic neurons including sensitization and desensitization, priming, and shift of neuronal phenotype.

scholarly journals Epigenetic events in medulloblastoma development

2005 ◽  
Vol 19 (5) ◽  
pp. 1-13 ◽  
Author(s):  
Janet C. Lindsey ◽  
Jennifer A. Anderton ◽  
Meryl E. Lusher ◽  
Steven C. Clifford
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor Genes ◽  
Molecular Basis ◽  
Gene Disruption ◽  
Functional Role ◽  
Promoter Hypermethylation ◽  
Therapeutic Approaches ◽  
Primary Tumors ◽  
Molecular Events ◽  
Epigenetic Events

Over the last decade, the analysis of genetic defects in primary tumors has been central to the identification of molecular events and biological pathways involved in the pathogenesis of medulloblastoma, the most common malignant brain tumor of childhood. Despite this, understanding of the molecular basis of the majority of cases remains poor. In recent years, the emerging field of epigenetics, which describes heritable alterations in gene expression that occur in the absence of DNA sequence changes, has forced a revision of the understanding of the mechanisms of gene disruption in cancer. Accumulating evidence indicates a significant involvement for epigenetic events in medulloblastoma development. Recent studies have identified a series of candidate tumor suppressor genes (for example, RASSF1A, CASP8, and HIC1) that are each specifically epigenetically inactivated in a large proportion (> 30%) of medulloblastomas by promoter hypermethylation, leading to the silencing of their gene expression. These findings shed new light on medulloblastoma and offer great potential for an improved understanding of its molecular pathology. The authors review the current understanding of epigenetic events in cancer and their contribution to medulloblastoma development. Their nature, origins, and functional role(s) in tumorigenesis are considered, and the authors assess the potential utility of these events as a basis for novel diagnostic and therapeutic approaches.

Virtual screening of natural bioactives in combating cancer through epigenetic modulation

2011 ◽  
Vol 1 (5) ◽  
pp. 12-16
Author(s):  
Ravi Kapopara ◽  
S. Prasanth Kumar ◽  
S K Patel ◽  
D K Sadhu ◽  
Y T Jasrai ◽  
...  
Keyword(s):  
Cancer Biology ◽  
Histone H3 ◽  
Genetic Material ◽  
Dna Methyltransferases ◽  
Methyl Transferase ◽  
Computational Screening ◽  
Histone Deacetylase 8 ◽  
Epigenetic Events ◽  
Altered Gene ◽  
Epigenetic Modulation

Epigenetic events are due to altered gene expression without any changes inthe genetic material and characteristic of heritability via cell division. Theimpact of epigenetic control over cancer is one among the thrust area ofresearch in cancer biology. The present study deals about the virtual screeningof plant derived bioactives, directed against the key molecular regulatorsof the epigenetic events viz. DNA methyltransferases (DNMT1, DNMT2 andDNMT3B), Histone acetyltransferase (HAT), Histone deacetylase 8 (HDAC8),Histone H3 lysine 27 methyl transferase (H3K27MT) and Histone H3 specificlysine 4 demethylase (H3K4DM). This computational screening identifies themost efficient binders with respect to individual targets in terms of ligandbinding energy. The structure optimization of the best scored docked conformationswill be helpful to reveal new insights and development of naturalbioactives to combat cancer.

scholarly journals Molecular Events Involved in Influenza A Virus-Induced Cell Death

2022 ◽  
Vol 12 ◽  
Author(s):  
Rui Gui ◽  
Quanjiao Chen
Keyword(s):  
Cell Death ◽  
Influenza A Virus ◽  
Influenza A ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Tissue Destruction ◽  
Inflammatory Reactions ◽  
Molecular Events ◽  
Host Death

Viral infection usually leads to cell death. Moderate cell death is a protective innate immune response. By contrast, excessive, uncontrolled cell death causes tissue destruction, cytokine storm, or even host death. Thus, the struggle between the host and virus determines whether the host survives. Influenza A virus (IAV) infection in humans can lead to unbridled hyper-inflammatory reactions and cause serious illnesses and even death. A full understanding of the molecular mechanisms and regulatory networks through which IAVs induce cell death could facilitate the development of more effective antiviral treatments. In this review, we discuss current progress in research on cell death induced by IAV infection and evaluate the role of cell death in IAV replication and disease prognosis.

scholarly journals Spatiotemporal Dynamics of Molecular Pathology in Amyotrophic Lateral Sclerosis

2018 ◽  
Author(s):  
Silas Maniatis ◽  
Tarmo Äijö ◽  
Sanja Vickovic ◽  
Catherine Braine ◽  
Kristy Kang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Molecular Mechanisms ◽  
Early Time ◽  
Spatiotemporal Dynamics ◽  
Course Of Disease ◽  
Molecular Events ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractParalysis occurring in amyotrophic lateral sclerosis (ALS) results from denervation of skeletal muscle as a consequence of motor neuron degeneration. Interactions between motor neurons and glia contribute to motor neuron loss, but the spatiotemporal ordering of molecular events that drive these processes in intact spinal tissue remains poorly understood. Here, we use spatial transcriptomics to obtain gene expression measurements of mouse spinal cords over the course of disease, as well as of postmortem tissue from ALS patients, to characterize the underlying molecular mechanisms in ALS. We identify novel pathway dynamics, regional differences between microglia and astrocyte populations at early time-points, and discern perturbations in several transcriptional pathways shared between murine models of ALS and human postmortem spinal cords.One Sentence SummaryAnalysis of the ALS spinal cord using Spatial Transcriptomics reveals spatiotemporal dynamics of disease driven gene regulation.

scholarly journals Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators

2019 ◽  
Author(s):  
Ru-pin Alicia Chi ◽  
Tianyuan Wang ◽  
Nyssa Adams ◽  
San-pin Wu ◽  
Steven L. Young ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rna Seq ◽  
Uterine Receptivity ◽  
Normal Cycle ◽  
Estrogen Response ◽  
Molecular Events ◽  
History Of ◽  
And Function ◽  
Genomic Regions ◽  
Fertile Women

ABSTRACTContextPoor uterine receptivity is one major factor leading to pregnancy loss and infertility. Understanding the molecular events governing successful implantation is hence critical in combating infertility.ObjectiveTo define PGR-regulated molecular mechanisms and epithelial roles in receptivity.DesignRNA-seq and PGR-ChIP-seq were conducted in parallel to identify PGR-regulated pathways during the WOI in endometrium of fertile women.SettingEndometrial biopsies from the proliferative and mid-secretory phases were analyzed.Patients or Other ParticipantsParticipants were fertile, reproductive aged (18-37) women with normal cycle length; and without any history of dysmenorrhea, infertility, or irregular cycles. In total, 42 endometrial biopsies obtained from 42 women were analyzed in this study.InterventionsThere were no interventions during this study.Main Outcome MeasuresHere we measured the alterations in gene expression and PGR occupancy in the genome during the WOI, based on the hypothesis that PGR binds uterine chromatin cycle-dependently to regulate genes involved in uterine cell differentiation and function.Results653 genes were identified with regulated PGR binding and differential expression during the WOI. These were involved in regulating inflammatory response, xenobiotic metabolism, EMT, cell death, interleukin/STAT signaling, estrogen response, and MTORC1 response. Transcriptome of the epithelium identified 3,052 DEGs, of which 658 were uniquely regulated. Transcription factors IRF8 and MEF2C were found to be regulated in the epithelium during the WOI at the protein level, suggesting potentially important functions that are previously unrecognized.ConclusionPGR binds the genomic regions of genes regulating critical processes in uterine receptivity and function.PrécisUsing a combination of RNA-seq and PGR ChIP-seq, novel signaling pathways and epithelial regulators were identified in the endometrium of fertile women during the window of implantation.

Gamma-Band Auditory Steady-State Response as a Neurophysiological Marker for Excitation and Inhibition Balance: A Review for Understanding Schizophrenia and Other Neuropsychiatric Disorders

2019 ◽  
Vol 51 (4) ◽  
pp. 234-243 ◽  
Author(s):  
Mariko Tada ◽  
Kenji Kirihara ◽  
Daisuke Koshiyama ◽  
Mao Fujioka ◽  
Kaori Usui ◽  
...  
Keyword(s):  
Steady State ◽  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Neuropsychiatric Disorders ◽  
Gamma Oscillations ◽  
Developmental Trajectory ◽  
Clinical Staging ◽  
Steady State Response ◽  
State Response ◽  
Auditory Steady State Response

Altered gamma oscillations have attracted considerable attention as an index of the excitation/inhibition (E/I) imbalance in schizophrenia and other neuropsychiatric disorders. The auditory steady-state response (ASSR) has been the most robust probe of abnormal gamma oscillatory dynamics in schizophrenia. Here, we review recent ASSR studies in patients with schizophrenia and other neuropsychiatric disorders. Preclinical ASSR research, which has contributed to the elucidation of the underlying pathophysiology of these diseases, is also discussed. The developmental trajectory of the ASSR has been explored and may show signs of the maturation and disruption of E/I balance in adolescence. Animal model studies have shown that synaptic interactions between parvalbumin-positive GABAergic interneurons and pyramidal neurons contribute to the regulation of E/I balance, which is related to the generation of gamma oscillation. Therefore, ASSR alteration may be a significant electrophysiological finding related to the E/I imbalance in neuropsychiatric disorders, which is a cross-disease feature and may reflect clinical staging. Future studies regarding ASSR generation, especially in nonhuman primate models, will advance our understanding of the brain circuit and the molecular mechanisms underlying neuropsychiatric disorders.

scholarly journals Drosophila Neuronal Injury Follows a Temporal Sequence of Cellular Events Leading to Degeneration at the Neuromuscular Junction

2015 ◽  
Vol 9s2 ◽  
pp. JEN.S25516 ◽  
Author(s):  
Barron L. Lincoln ◽  
Sahar H. Alabsi ◽  
Nicholas Frendo ◽  
Robert Freund ◽  
Lani C. Keller
Keyword(s):  
Neuromuscular Junction ◽  
Model Organism ◽  
Structural Defects ◽  
Cellular Mechanisms ◽  
Post Injury ◽  
Ubiquitinated Proteins ◽  
Cellular Events ◽  
Molecular Events ◽  
Complex Signaling

Neurodegenerative diseases affect millions of people worldwide, and as the global population ages, there is a critical need to improve our understanding of the molecular and cellular mechanisms that drive neurodegeneration. At the molecular level, neurodegeneration involves the activation of complex signaling pathways that drive the active destruction of neurons and their intracellular components. Here, we use an in vivo motor neuron injury assay to acutely induce neurodegeneration in order to follow the temporal order of events that occur following injury in Drosophila melanogaster. We find that sites of injury can be rapidly identified based on structural defects to the neuronal cytoskeleton that result in disrupted axonal transport. Additionally, the neuromuscular junction accumulates ubiquitinated proteins prior to the neurodegenerative events, occurring at 24 hours post injury. Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism. Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans. Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments.

A study of the molecular–cellular interface in visual photoreceptors by light scattering photometry

1985 ◽  
Vol 63 (7) ◽  
pp. 1933-1939 ◽  
Author(s):  
T. Borys ◽  
S. Deshpande ◽  
R. Jones ◽  
E. W. Abrahamson
Keyword(s):  
Light Scattering ◽  
Structural Changes ◽  
Time Range ◽  
Relaxation Techniques ◽  
Cell Organelles ◽  
Whole Cells ◽  
Cellular Events ◽  
Molecular Events ◽  
Cytological Changes ◽  
Non Destructive

The correlation of molecular events with structural changes within the cell requires a non-destructive relaxation technique that can be adapted to measure such cellular changes in a time range of milliseconds to minutes. Light scattering relaxation techniques have proved useful for such studies as they can often be measured simultaneously or in parallel with absorption or fluorescence spectral changes characterizing molecular or macromolecular processes. Such techniques are proving useful in the study of photobiological processes such as visual photoreception where specific cytological changes produced photochemically can be effected by alternate controlled perturbations such as osmotic shrinking or swelling of cell organelles and (or) whole cells. This paper illustrates how light scattering relaxation spectrophotometry can be applied to the correlation of molecular and cellular events in visual photoreceptors.

Experimental manipulation of cerebral cortical areas in primates

1991 ◽  
Vol 331 (1261) ◽  
pp. 291-294 ◽  
Keyword(s):  
Molecular Mechanisms ◽  
Experimental Manipulation ◽  
Cognitive Capacity ◽  
Brain Functions ◽  
Cortical Areas ◽  
Cellular Events ◽  
Species Specific ◽  
Higher Brain Functions ◽  
Synaptic Circuitry ◽  
Cytoarchitectonic Areas

The developmental mechanisms underlying the subdivision of the neocortex into structurally and functionally distinct areas is central to our understanding of the development of human cognitive capacity and the pathogenesis of congenital disorders of higher brain functions. The protomap hypothesis suggests how the cytoarchitectonic pattern of the cerebral cortex may be generated by a combination of intrinsic and extrinsic influences during embryonic development. Although little is known about the genetic and molecular mechanisms underlying this individual and species-specific diversity of cellular and synaptic architecture, experimental manipulation of development in the primate embryo provides a glimpse into the cascade of cellular events involved in the control of cell numbers, specification of neuronal phenotypes, their apportions into cytoarchitectonic areas, and establishment of area-specific synaptic circuitry.

scholarly journals Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽  
2020 ◽  
Author(s):  
Kaitlyn A Dorsett ◽  
Michael P Marciel ◽  
Jihye Hwang ◽  
Katherine E Ankenbauer ◽  
Nikita Bhalerao ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Sialic Acids ◽  
Invasion Resistance ◽  
Cell Behaviors ◽  
Molecular Events ◽  
Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

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