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Progress in Molecular Biology and Translational Science

Elad Lax, Moshe Szyf
Drug addiction is a devastating health problem that is a very heavy burden on the individual affected and the society in general. Recent research defines addiction as a neurobehavioral disorder. Underpinning biological mechanisms of drug addiction are abnormal neuronal and brain activity following acute and repeated drug exposure. Abnormal gene expression is found in reward and decision-making brain regions of addicts and in animal models and is possibly responsible for changes in brain function. DNA methylation is an epigenetic modification that regulates gene expression...
2018: Progress in Molecular Biology and Translational Science
Rochelle L Coulson, Janine M LaSalle
DNA sequence information alone cannot account for the immense variability between chromosomal alleles within diverse cell types in the brain, whether these differences are observed across time, cell type, or parental origin. The complex control and maintenance of gene expression and modulation are regulated by a multitude of molecular and cellular mechanisms that layer on top of the genetic code. The integration of genetic and environmental signals required for regulating brain development and function is achieved in part by a dynamic epigenetic landscape that includes DNA methylation, histone modifications, and noncoding RNAs...
2018: Progress in Molecular Biology and Translational Science
Catherine J Peña, Eric J Nestler
Depression is a prevalent and complex psychiatric syndrome. Epigenetic mechanisms bridge the genetic and environmental factors that contribute to the pathophysiology of depression. A surge of research over the last decade has identified changes in DNA methylation, histone modifications, histone organization, and noncoding RNAs associated with depression and stress-induced depression-like behavior in animal models. We focus here on associations of epigenetic factors concurrent with depression and depression-like behavior, although risk for depression and some of the associated epigenetic changes are known to have developmental origins...
2018: Progress in Molecular Biology and Translational Science
Sarah Barnett Burns, Daniel Almeida, Gustavo Turecki
Adverse experiences during sensitive postnatal developmental periods can disrupt the calibration of fundamental systems and increase the risk of a wide range of adult disease states, including psychiatric illnesses. Accumulating evidence suggests that epigenetic modifications involving DNA methylation, posttranslational histone modifications, and noncoding RNAs may be a key mediating factor in this disruption. Accumulating evidence from both animal models and human studies suggests that early life adversity alters the epigenome at multiple loci across the genome, but that the specific alterations, and the associated transcriptomic and psychiatric outcomes may be dependent on multiple individual factors...
2018: Progress in Molecular Biology and Translational Science
Amanda H Mahnke, Nihal A Salem, Alexander M Tseng, Dae D Chung, Rajesh C Miranda
Early developmental exposure to ethanol, a known teratogen, can result in a range of neurodevelopmental disorders, collectively referred to as Fetal Alcohol Spectrum Disorders (FASDs). Changes in the environment, including exposure to teratogens, can result in long term alterations to the epigenetic landscape of a cell, thereby altering gene expression. Noncoding RNAs (ncRNAs) can affect transcription and translation of networks of genes. ncRNAs are dynamically expressed during development and have been identified as a target of alcohol...
2018: Progress in Molecular Biology and Translational Science
Nagalakshmi B, Sneha Sagarkar, Amul J Sakharkar
Of all types of injuries, traumatic brain injuries (TBIs) are most likely to result in death or permanent physical or mental disabilities. With the increased frequency of military operations, terror attacks, sports activities, and road mishaps, TBIs are increasingly becoming a serious public health concern. Patients who meet with moderate-to-severe TBI suffer from a constellation of cognitive deficits and phenotypes due to diffuse axonal injury. On the contrary, minimal TBI precipitates in long-term behavioral complications commonly referred to as post-traumatic stress disorders, which consist of depression, anxiety, hallucinations, and so on...
2018: Progress in Molecular Biology and Translational Science
Bhaskar Roy, Yogesh Dwivedi
Stressful life incidents often cause a predisposition for developing mental disorders such as major depressive disorder (MDD). Impaired neurocognitive and neuro-vegetative functions of the central nervous system are the hallmarks of this mental illness. Blunted responses from emotionally salient regions of the brain including cortex, hippocampus, and amygdala have been associated with MDD-related behavioral changes. Moreover, improper signal processing and neuronal atrophy were held responsible for the overall dysfunctionality of these vulnerable regions in the MDD brain...
2018: Progress in Molecular Biology and Translational Science
Prashanth Rajarajan, Yan Jiang, Bibi S Kassim, Schahram Akbarian
Chromosomal conformations, including promoter-enhancer loops, provide a critical regulatory layer for the transcriptional machinery. Therefore, schizophrenia, a common psychiatric disorder associated with broad changes in neuronal gene expression in prefrontal cortex and other brain regions implicated in psychosis, could be associated with alterations in higher-order chromatin. Here, we review early studies on spatial genome organization in the schizophrenia postmortem brain and discuss how integrative approaches using cell culture and animal model systems could gain deeper insight into the potential roles of higher-order chromatin for the neurobiology of and novel treatment avenues for common psychiatric disease...
2018: Progress in Molecular Biology and Translational Science
Chunyu Liu, Chuan Jiao, Kangli Wang, Ning Yuan
DNA methylation has been an important area of research in the study of molecular mechanism to psychiatric disorders. Recent evidence has suggested that abnormalities in global methylation, methylation of genes, and pathways could play a role in the etiology of many forms of mental illness. In this article, we review the mechanisms of DNA methylation, including the genetic and environmental factors affecting methylation changes. We report and discuss major findings regarding DNA methylation in psychiatric patients, both within the context of global methylation studies and gene-specific methylation studies...
2018: Progress in Molecular Biology and Translational Science
Jacob Peedicayil, Aniket Kumar
There is increasing evidence that changes in epigenetic mechanisms of gene expression are involved in the pathogenesis of mood disorders. Such evidence stems from studies conducted on postmortem brain tissues and peripheral cells or tissues of patients with mood disorders. This article describes and discusses the epigenetic changes in the mood disorders (major depressive disorder and bipolar disorder) found to date. The article also describes and discusses preclinical drug trials of epigenetic drugs for treating mood disorders...
2018: Progress in Molecular Biology and Translational Science
Reema Abdulrahman S Alyamani, Chris Murgatroyd
Studies show that adverse conditions during early life can increase risks of developing mood disorders later in life. It is currently hypothesized that levels of environmental adversity in this early developmental period are able to shape the experience-dependent maturation of stress-regulating pathways leading to long-lasting alterations in stress responsivity during adulthood; a phenomenon often referred to as "early-life programming." Research is addressing the molecular mechanisms underlying this programming by which gene-environment interactions can predispose individuals toward psychopathology...
2018: Progress in Molecular Biology and Translational Science
Dennis R Grayson, Alessandro Guidotti
Schizophrenia (SZ) is a debilitating disease that impacts 1% of the population worldwide. Association studies have shown that inherited genetic mutations account for a portion of disease risk. However, environmental factors play an important role in the pathophysiology of the disease by altering cellular epigenetic marks at the level of chromatin. Postmortem brain studies of SZ subjects suggest that the dynamic equilibrium between DNA methylation and demethylation network components is disrupted at the level of individual SZ target genes...
2018: Progress in Molecular Biology and Translational Science
Tiffany S Doherty, Tania L Roth
It is understood that adversity during development has the power to alter behavioral trajectories, and the role of the epigenome in that relationship is currently under intense investigation. Several studies in both nonhuman animals and humans have established a link between early adversity and epigenetic regulation of genes heavily implicated in the stress response, plasticity and cognition, and psychiatric disorders such as depression and anxiety. Thus the relatively recent surge of studies centering on the epigenetic outcomes of stress has great potential to inform treatments and interventions for psychiatric disorder precipitated by early adversity...
2018: Progress in Molecular Biology and Translational Science
Ronald L Schnaar, Pablo H H Lopez
No abstract text is available yet for this article.
2018: Progress in Molecular Biology and Translational Science
Sandro Sonnino, Elena Chiricozzi, Sara Grassi, Laura Mauri, Simona Prioni, Alessandro Prinetti
Since the structure of GM1 was elucidated 55years ago, researchers have been attracted by the sialylated glycans of gangliosides. Gangliosides head groups, protruding toward the extracellular space, significantly contribute to the cell glycocalyx; and in certain cells, such as neurons, are major determinants of the features of the cell surface. Expression of glycosyltransferases involved in the de novo biosynthesis of gangliosides is tightly regulated along cell differentiation and activation, and is regarded as the main metabolic mechanism responsible for the acquisition of cell-specific ganglioside patterns...
2018: Progress in Molecular Biology and Translational Science
T August Li, Ronald L Schnaar
Gangliosides are expressed on all vertebrate cells and tissues, but are particularly abundant in the mammalian brain, where they constitute major cell-surface determinants on all nerve cells. The same four ganglioside structures, GM1, GD1a, GD1b, and GT1b, constitute the great majority of brain gangliosides in all mammals. Biosynthesis of these major brain gangliosides starts with addition of glucose to the ceramide lipid carrier followed by stepwise addition of up to six additional monosaccharides. This primarily involves the sequential action of seven glycosyltransferases, many of which appear to act specifically on glycolipid (rather than glycoprotein) acceptors...
2018: Progress in Molecular Biology and Translational Science
Robert W Ledeen, Gusheng Wu
This review addresses the role of α-synuclein (αSyn) in the etiopathology of Parkinson's disease (PD), with emphasis on its interaction with GM1 ganglioside. We begin with a brief review of some of the milestone discoveries that helped to elucidate PD neuropathology, including the fibrous inclusions of Lewy that characterize the degenerating dopaminergic neurons of the substantia nigra and the presence of αSyn as a major constituent of these Lewy bodies and neurites. This enabled Braak et al. to define the progressive nature of PD in developing their staging hypothesis which described the topographically predictable sequence of neuropathological changes giving rise to prodromal nonmotor symptoms that precede the classical motor dysfunctions...
2018: Progress in Molecular Biology and Translational Science
Katsumi Matsuzaki, Koichi Kato, Katsuhiko Yanagisawa
Assembly and deposition of amyloid β-protein (Aβ) is an early and invariable pathological event of Alzheimer's disease (AD), a chronic neurodegenerative disease affecting the neurons in the brain of aging population. Thus, clarification of the molecular mechanism underlying Aβ assembly is crucial not only for understanding the pathogenesis of AD, but also for developing disease-modifying remedies. In 1995, ganglioside-bound Aβ (GAβ), with unique molecular characteristics, including its altered immunoreactivity and its conspicuous ability to accelerate Aβ assembly, was discovered in an autopsied brain showing early pathological changes of AD...
2018: Progress in Molecular Biology and Translational Science
Pablo H H Lopez, Bárbara Beatriz Báez
Gangliosides are a family of sialic acid-containing glycosphingolipids highly expressed in the nervous system of vertebrates. Over the last 25years, research has unmasked several of their neurobiological functions but the role of gangliosides in the nervous system remains not fully elucidated. Genetic disruption of genes for key enzymes involved in ganglioside biosynthesis led to the discovery of their diverse functions and highlighted the exquisite structural specificity required in this processes. In the nervous system, gangliosides regulate axonal caliber and organize ion channels at the nodes of Ranvier, a critical step to ensure fast conduction velocity of myelinated fibers...
2018: Progress in Molecular Biology and Translational Science
John A Goodfellow, Hugh J Willison
A wide range of neuroimmunological diseases, referred to as autoimmune neuropathies, affect the peripheral nervous systems (PNS). The PNS is structurally diverse with complex anatomical compartments enriched in many different myelin and neuronal glycolipids, notably gangliosides. Autoimmune neuropathies are a proportion of autoimmune neuropathies mediated by autoimmune attack due to antibodies reactive with these compartmentally localized gangliosides. Antiganglioside antibodies are principally associated with the acute paralytic disease, Guillain-Barré syndrome, and are also found in several chronic autoimmune neuropathy syndromes...
2018: Progress in Molecular Biology and Translational Science
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