scholarly journals Regulatory networks between Polycomb complexes and non-coding RNAs in the central nervous system

2019 ◽  
Vol 12 (5) ◽  
pp. 327-336
Author(s):  
Ya-Jie Xu ◽  
Pei-Pei Liu ◽  
Shyh-Chang Ng ◽  
Zhao-Qian Teng ◽  
Chang-Mei Liu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Development ◽  
Regulatory Networks ◽  
High Throughput Sequencing ◽  
Neuronal Development ◽  
Polycomb Group ◽  
Functional Roles ◽  
Cellular Processes ◽  
Non Coding Rnas

Abstract High-throughput sequencing has facilitated the identification of many types of non-coding RNAs (ncRNAs) involved in diverse cellular processes. NcRNAs as epigenetic mediators play key roles in neuronal development, maintenance, and dysfunction by controlling gene expression at multiple levels. NcRNAs may not only target specific DNA or RNA for gene silence but may also directly interact with chromatin-modifying proteins like Polycomb group (PcG) proteins to drive orchestrated transcriptional programs. Recent significant progress has been made in characterizing ncRNAs and PcG proteins involved in transcriptional, post-transcriptional, and epigenetic regulation. More importantly, dysregulation of ncRNAs, PcG proteins, and interplay among them is closely associated with the pathogenesis of central nervous system (CNS) disorders. In this review, we focus on the interplay between ncRNAs and PcG proteins in the CNS and highlight the functional roles of the partnership during neural development and diseases.

scholarly journals Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aya Mikdache ◽  
Marie-José Boueid ◽  
Lorijn van der Spek ◽  
Emilie Lesport ◽  
Brigitte Delespierre ◽  
...  
Keyword(s):  
Nervous System ◽  
G Protein ◽  
Neural Development ◽  
Neuronal Development ◽  
Axon Outgrowth ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Loss Of Function ◽  
G Protein Coupled

AbstractThe Regulator of G protein signaling 4 (Rgs4) is a member of the RGS proteins superfamily that modulates the activity of G-protein coupled receptors. It is mainly expressed in the nervous system and is linked to several neuronal signaling pathways; however, its role in neural development in vivo remains inconclusive. Here, we generated and characterized a rgs4 loss of function model (MZrgs4) in zebrafish. MZrgs4 embryos showed motility defects and presented reduced head and eye sizes, reflecting defective motoneurons axon outgrowth and a significant decrease in the number of neurons in the central and peripheral nervous system. Forcing the expression of Rgs4 specifically within motoneurons rescued their early defective outgrowth in MZrgs4 embryos, indicating an autonomous role for Rgs4 in motoneurons. We also analyzed the role of Akt, Erk and mechanistic target of rapamycin (mTOR) signaling cascades and showed a requirement for these pathways in motoneurons axon outgrowth and neuronal development. Drawing on pharmacological and rescue experiments in MZrgs4, we provide evidence that Rgs4 facilitates signaling mediated by Akt, Erk and mTOR in order to drive axon outgrowth in motoneurons and regulate neuronal numbers.

Understanding cellular glycan surfaces in the central nervous system

2018 ◽  
Vol 47 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Sameera Iqbal ◽  
Mina Ghanimi Fard ◽  
Arun Everest-Dass ◽  
Nicolle H. Packer ◽  
Lindsay M. Parker
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Development ◽  
Analytical Techniques ◽  
Detection Methods ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Enzymatic Process ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Abstract Glycosylation, the enzymatic process by which glycans are attached to proteins and lipids, is the most abundant and functionally important type of post-translational modification associated with brain development, neurodegenerative disorders, psychopathologies and brain cancers. Glycan structures are diverse and complex; however, they have been detected and targeted in the central nervous system (CNS) by various immunohistochemical detection methods using glycan-binding proteins such as anti-glycan antibodies or lectins and/or characterized with analytical techniques such as chromatography and mass spectrometry. The glycan structures on glycoproteins and glycolipids expressed in neural stem cells play key roles in neural development, biological processes and CNS maintenance, such as cell adhesion, signal transduction, molecular trafficking and differentiation. This brief review will highlight some of the important findings on differential glycan expression across stages of CNS cell differentiation and in pathological disorders and diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, schizophrenia and brain cancer.

scholarly journals Tuberin levels during cellular differentiation in brain development

2021 ◽  
Author(s):  
Bashaer Abu Khatir ◽  
Gordon Omar Davis ◽  
Mariam Sameem ◽  
Rutu Patel ◽  
Jackie Fong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cell Lines ◽  
Neural Development ◽  
Time Course ◽  
Embryonic Mouse ◽  
Organ Systems ◽  
The Central Nervous System

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex, and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, lead to the formation of tumors and developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that Tuberin levels remain stable in the olfactory bulb but decrease in the Purkinje cell layer during embryonic mouse brain development. We show here that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. These data provide support for the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.

scholarly journals MicroRNA Signature in Human Normal and Tumoral Neural Stem Cells

2019 ◽  
Vol 20 (17) ◽  
pp. 4123 ◽  
Author(s):  
Diana ◽  
Gaido ◽  
Murtas
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Mature Mirnas ◽  
Human Species ◽  
Cellular Context ◽  
The Central Nervous System ◽  
Non Coding Rnas ◽  
Insight Into

MicroRNAs, also called miRNAs or simply miR-, represent a unique class of non-coding RNAs that have gained exponential interest during recent years because of their determinant involvement in regulating the expression of several genes. Despite the increasing number of mature miRNAs recognized in the human species, only a limited proportion is engaged in the ontogeny of the central nervous system (CNS). miRNAs also play a pivotal role during the transition of normal neural stem cells (NSCs) into tumor-forming NSCs. More specifically, extensive studies have identified some shared miRNAs between NSCs and neural cancer stem cells (CSCs), namely miR-7, -124, -125, -181 and miR-9, -10, -130. In the context of NSCs, miRNAs are intercalated from embryonic stages throughout the differentiation pathway in order to achieve mature neuronal lineages. Within CSCs, under a different cellular context, miRNAs perform tumor suppressive or oncogenic functions that govern the homeostasis of brain tumors. This review will draw attention to the most characterizing studies dealing with miRNAs engaged in neurogenesis and in the tumoral neural stem cell context, offering the reader insight into the power of next generation miRNA-targeted therapies against brain malignances.

Investigating the Tissue Specific Expression Patterns of Murine Semaphorins 3C, 4D, 4G, 6A and 7A in Primary Lymphoid Tissues

2001 ◽  
Vol 7 (S2) ◽  
pp. 76-77
Author(s):  
Sreedevi Chalasani ◽  
David Matthes
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cell Survival ◽  
Neuronal Development ◽  
Expression Patterns ◽  
Human Neutrophils ◽  
Lymphoid Tissues ◽  
Specific Expression ◽  
Est Analysis

Semaphorins are primarily known for the important role they play in the guidance of growth cones during neuronal development. There is evidence, however, that semaphorins are expressed outside the nervous system as well, suggesting a wider scope for semaphorin function. The overall objective of our study is to identify the functions of semaphorins outside central nervous system especially in T cell development. Some of the 20 semaphorins have been shown to have extra-neural functions that include (for different semaphorins) bone differentiation, promotion of B-cell survival and aggregation, and activation of T-cells. Apart from central nervous system statement of most semaphorins, one semaphorin (CD 100) has transcripts in T cells, B cells, neutrophils, monocytes and granulocytes. EST analysis suggests that other semaphorins are expressed in lymphoid tissues such as thymus, spleen, tonsil, and the interfollicular areas and germinal centers of lymph nodes.Semaphorins have been related to several cell survival mechanisms, immunosuppression and promotion of cell death resistance. in preliminary studies our lab found that viral semaphorins inhibit the migration of human T cells and human SEMA3A can inhibit migration of human neutrophils.

scholarly journals H2S-based therapies for ischaemic stroke: opportunities and challenges

2019 ◽  
Vol 4 (2) ◽  
pp. 63-66 ◽  
Author(s):  
Jia Jia ◽  
Jie Li ◽  
Jian Cheng
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ischaemic Stroke ◽  
Stroke Patients ◽  
Stroke Outcomes ◽  
Mortality And Morbidity ◽  
Functional Roles ◽  
Cellular Models ◽  
Signalling Molecule ◽  
The Central Nervous System

Stroke is a cerebrovascular disease displaying high mortality and morbidity. Despite extensive efforts, only very few therapies are available for stroke patients as yet. Hydrogen sulfide (H2S) is thought to be a signalling molecule that is endogenously produced and plays functional roles in the central nervous system. Currently, numerous studies show that H2S impacts stroke outcomes in animal and cellular models. Here, we review the recent research regarding the effects of endogenously produced H2S as well as exogenous H2S donors on stroke pathology, focusing on the potential of H2S-based therapies in treating ischaemic stroke. We also discuss the several issues that hinder the clinical translation of H2S-based therapies from the bench. Taken together, we think that H2S-based therapies are promising strategies for treating cerebral ischaemia if we successfully address these issues.

scholarly journals Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications

2019 ◽  
Vol 20 (4) ◽  
pp. 974 ◽  
Author(s):  
Valeria Gasperi ◽  
Matteo Sibilano ◽  
Isabella Savini ◽  
Maria Catani
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nicotinamide Adenine Dinucleotide ◽  
Cell Cycle Progression ◽  
Neuronal Development ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nicotinamide Adenine ◽  
Vitamin B3 ◽  
Traumatic Injuries ◽  
The Central Nervous System

Niacin (also known as “vitamin B3” or “vitamin PP”) includes two vitamers (nicotinic acid and nicotinamide) giving rise to the coenzymatic forms nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The two coenzymes are required for oxidative reactions crucial for energy production, but they are also substrates for enzymes involved in non-redox signaling pathways, thus regulating biological functions, including gene expression, cell cycle progression, DNA repair and cell death. In the central nervous system, vitamin B3 has long been recognized as a key mediator of neuronal development and survival. Here, we will overview available literature data on the neuroprotective role of niacin and its derivatives, especially focusing especially on its involvement in neurodegenerative diseases (Alzheimer’s, Parkinson’s, and Huntington’s diseases), as well as in other neuropathological conditions (ischemic and traumatic injuries, headache and psychiatric disorders).

scholarly journals Death of developing neurons: New insights and implications for connectivity

2013 ◽  
Vol 203 (3) ◽  
pp. 385-393 ◽  
Author(s):  
Martijn P.J. Dekkers ◽  
Vassiliki Nikoletopoulou ◽  
Yves-Alain Barde
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Growth Factors ◽  
Axonal Degeneration ◽  
Neuronal Development ◽  
Critical Role ◽  
Synaptic Function ◽  
The Central Nervous System ◽  
Developing Neurons

The concept that target tissues determine the survival of neurons has inspired much of the thinking on neuronal development in vertebrates, not least because it is supported by decades of research on nerve growth factor (NGF) in the peripheral nervous system (PNS). Recent discoveries now help to understand why only some developing neurons selectively depend on NGF. They also indicate that the survival of most neurons in the central nervous system (CNS) is not simply regulated by single growth factors like in the PNS. Additionally, components of the cell death machinery have begun to be recognized as regulators of selective axonal degeneration and synaptic function, thus playing a critical role in wiring up the nervous system.

scholarly journals The Effect of Melatonin Modulation of Non-coding RNAs on Central Nervous System Disorders: An Updated Review

2020 ◽  
Vol 19 (1) ◽  
pp. 3-23
Author(s):  
Jianan Lu ◽  
Yujie Luo ◽  
Shuhao Mei ◽  
Yuanjian Fang ◽  
Jianmin Zhang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Circular Rna ◽  
Future Research ◽  
Protective Function ◽  
Messenger Ribonucleic Acid ◽  
Wide Range ◽  
The Central Nervous System ◽  
Non Coding Rnas ◽  
Regulatory Effects

: Melatonin is a hormone produced in and secreted by the pineal gland. Besides its role in regulating circadian rhythms, melatonin has a wide range of protective functions in the central nervous system (CNS) disorders. The mechanisms underlying this protective function are associated with the regulatory effects of melatonin on related genes and proteins. In addition to messenger ribonucleic acid (RNA) that can be translated into protein, an increasing number of non-coding RNAs in the human body are proven to participate in many diseases. This review discusses the current progress of research on the effects of melatonin modulation of non-coding RNAs (ncRNAs), including microRNA, long ncRNA, and circular RNA. The role of melatonin in regulating common pathological mechanisms through these ncRNAs is also summarized. Furthermore, the ncRNAs, currently shown to be involved in melatonin signaling in CNS diseases, are discussed. The information compiled in this review will open new avenues for future research into melatonin mechanisms and provide a further understanding of ncRNAs in the CNS.

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