Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Roles of NF-kappaB in central nervous system damage and repair.

ABSTRACT: NF-kappaB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin kappa-chain enhancer and enhance transcriptional activity. NF-kappaB/Rel proteins, as a dimeric transcription factor, control the expression of genes that regulate a broad range of biological processes through canonical and non-canonical pathways. In the central nervous system, NF-kappaB controls inflammatory reactions and the apoptotic cell death following nerve injury. It also contributes to the infarction and cell death in stroke models and patients. However, NF-kappaB is essential for neurosurvival as well. NF-kappaB activation is a part of recovery process that may protect neurons against oxidative-stresses or brain ischemia-induced apoptosis and neurodegeneration. Inhibition of NF-kappaB may reduce its neuroprotection activity. Hence the dual opposite effects of NF-kappaB on cells. The ultimate survival or death of neurons depends on which, where and when the NF-kappaB factors are activated.

SUBMITTER: Yang L

PROVIDER: S-EPMC5550580 | biostudies-other | 2007 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Chromatin regulation of DNA damage repair and genome integrity in the central nervous system.

Project description:With the continued extension of lifespan, aging and age-related diseases have become a major medical challenge to our society. Aging is accompanied by changes in multiple systems. Among these, the aging process in the central nervous system is critically important but very poorly understood. Neurons, as post-mitotic cells, are devoid of replicative associated aging processes, such as senescence and telomere shortening. However, because of the inability to self-replenish, neurons have to withstand challenge from numerous stressors over their lifetime. Many of these stressors can lead to damage of the neurons' DNA. When the accumulation of DNA damage exceeds a neuron's capacity for repair, or when there are deficiencies in DNA repair machinery, genome instability can manifest. The increased mutation load associated with genome instability can lead to neuronal dysfunction and ultimately to neuron degeneration. In this review, we first briefly introduce the sources and types of DNA damage and the relevant repair pathways in the nervous system (summarized in Fig. 1). We then discuss the chromatin regulation of these processes and summarize our understanding of the contribution of genomic instability to neurodegenerative diseases.

| S-EPMC5560486 | biostudies-other

Pleiotropic Roles of P2X7 in the Central Nervous System.

Project description:The purinergic receptor P2X7 is expressed in neural and immune cells known to be involved in neurological diseases. Its ligand, ATP, is a signaling molecule that can act as a neurotransmitter in physiological conditions or as a danger signal when released in high amount by damaged/dying cells or activated glial cells. Thus, ATP is a danger-associated molecular pattern. Binding of ATP by P2X7 leads to the activation of different biochemical pathways, depending on the physiological or pathological environment. The aim of this review is to discuss various functions of P2X7 in the immune and central nervous systems. We present evidence that P2X7 may have a detrimental or beneficial role in the nervous system, in the context of neurological pathologies: epilepsy, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, age-related macular degeneration and cerebral artery occlusion.

| S-EPMC6738027 | biostudies-literature

IkappaB kinase 2 determines oligodendrocyte loss by non-cell-autonomous activation of NF-kappaB in the central nervous system.

Project description:The I?B kinase complex induces nuclear factor kappa B activation and has recently been recognized as a key player of autoimmunity in the central nervous system. Notably, I?B kinase/nuclear factor kappa B signalling regulates peripheral myelin formation by Schwann cells, however, its role in myelin formation in the central nervous system during health and disease is largely unknown. Surprisingly, we found that brain-specific I?B kinase 2 expression is dispensable for proper myelin assembly and repair in the central nervous system, but instead plays a fundamental role for the loss of myelin in the cuprizone model. During toxic demyelination, inhibition of nuclear factor kappa B activation by conditional ablation of I?B kinase 2 resulted in strong preservation of central nervous system myelin, reduced expression of proinflammatory mediators and a significantly attenuated glial response. Importantly, I?B kinase 2 depletion in astrocytes, but not in oligodendrocytes, was sufficient to protect mice from myelin loss. Our results reveal a crucial role of glial cell-specific I?B kinase 2/nuclear factor kappa B signalling for oligodendrocyte damage during toxic demyelination. Thus, therapies targeting I?B kinase 2 function in non-neuronal cells may represent a promising strategy for the treatment of distinct demyelinating central nervous system diseases.

| S-EPMC4055835 | biostudies-other

Interleukin-1? in Central Nervous System Injury and Repair.

Project description:Acute inflammation is a self-limiting, complex biological response mounted to combat pathogen invasion, to protect against tissue damage, and to promote tissue repair should it occur. However, unabated inflammation can be deleterious and contribute to injury and pathology. Interleukin-1? (IL-1?), a prototypical "pro-inflammatory" cytokine, is essential to cellular defense and tissue repair in nearly all tissues. With respect to brain, however, studies suggest that IL-1? has pleiotrophic effects. It acts as a neuromodulator in the healthy central nervous system (CNS), has been implicated in the pathogenic processes associated with a number of CNS maladies, but may also provide protection to the injured CNS. Here, we will review the physiological and pathophysiological functions of IL-1? in the central nervous system with regard to synaptic plasticity. With respect to disease, emphasis will be placed on stroke, epilepsy, Parkinson's disease and Alzheimer's disease where the ultimate injurious or reparative effects of IL-1? appear to depend on time, concentration and environmental milieu.

| S-EPMC4465544 | biostudies-other

The Emerging Roles for Telomerase in the Central Nervous System.

Project description:Telomerase, a specialized ribonucleoprotein enzyme complex, maintains telomere length at the 3' end of chromosomes, and functions importantly in stem cells, cancer and aging. Telomerase exists in neural stem cells (NSCs) and neural progenitor cells (NPCs), at a high level in the developing and adult brains of humans and rodents. Increasing studies have demonstrated that telomerase in NSCs/NPCs plays important roles in cell proliferation, neuronal differentiation, neuronal survival and neuritogenesis. In addition, recent works have shown that telomerase reverse transcriptase (TERT) can protect newborn neurons from apoptosis and excitotoxicity. However, to date, the link between telomerase and diseases in the central nervous system (CNS) is not well reviewed. Here, we analyze the evidence and summarize the important roles of telomerase in the CNS. Understanding the roles of telomerase in the nervous system is not only important to gain further insight into the process of the neural cell life cycle but would also provide novel therapeutic applications in CNS diseases such as neurodegenerative condition, mood disorders, aging and other ailments.

| S-EPMC5964194 | biostudies-literature

Central Nervous System Remyelination: Roles of Glia and Innate Immune Cells.

Project description:In diseases such as multiple sclerosis (MS), inflammation can injure the myelin sheath that surrounds axons, a process known as demyelination. The spontaneous regeneration of myelin, called remyelination, is associated with restoration of function and prevention of axonal degeneration. Boosting remyelination with therapeutic intervention is a promising new approach that is currently being tested in several clinical trials. The endogenous regulation of remyelination is highly dependent on the immune response. In this review article, we highlight the cell biology of remyelination and its regulation by innate immune cells. For the purpose of this review, we discuss the roles of microglia, and also astrocytes and oligodendrocyte progenitor cells (OPCs) as they are being increasingly recognized to have immune cell functions.

| S-EPMC6764409 | biostudies-literature

Use of polysialic acid in repair of the central nervous system.

Project description:Polysialic acid (PSA), a large cell-surface carbohydrate that regulates cell interactions, is used during vertebrate development to promote precursor cell migration and axon path-finding. The induction of PSA expression in damaged adult CNS tissues could help them to rebuild by creating conditions permissive for architectural remodeling. This possibility has been explored in two contexts, the regeneration of axons and the recruitment of endogenous neural precursors to a lesion. Glial scars that form at CNS injury sites block axon regeneration. It has been found that transfection of scar astrocytes by a viral vector encoding polysialyltransferase leads to sustained expression of high levels of PSA. With this treatment, a substantial portion of severed corticospinal tract axon processes were able to grow through a spinal injury site. In the studies of precursor cell migration to a cortical lesion, it was found that induced PSA expression in a path extending from the subventricular zone to a lesion near the cortical surface increased recruitment of BrdU/nestin-positive cells along the path and into the injury site. These displaced precursors were able to differentiate in a regionally appropriate manner. These findings suggest that induced PSA expression can be used as a strategy for promoting tissue repair involving both replacement of cells and rebuilding of neural connections.

| S-EPMC1636566 | biostudies-literature

Tissue plasminogen activator-independent roles of neuroserpin in the central nervous system.

Project description:A number of studies have confirmed the existence of tissue-type plasminogen activator-independent roles of neuroserpin, a member of the serine protease inhibitor superfamily. In this review article, we aim to clarify this role. These unique roles of neuroserpin are involved in its neuroprotective effect during ischemic brain injury, its regulation of tumorigenesis, and the mediation of emotion and cognition through the inhibition of urokinase-type plasminogen activator and fibrinolysin, modification of Th cells, reducing plaque formation, promoting process growth and intracellular adhesion, and altering the expression of cadherin and nuclear factor kappa B.

| S-EPMC4354132 | biostudies-literature

Differential roles of microglia and monocytes in the inflamed central nervous system.

Project description:In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell-mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood. In the present study, we addressed the cellular basis of autoimmune demyelination by discriminating microglial versus monocyte origins of effector macrophages. Using serial block-face scanning electron microscopy (SBF-SEM), we show that monocyte-derived macrophages associate with nodes of Ranvier and initiate demyelination, whereas microglia appear to clear debris. Gene expression profiles confirm that monocyte-derived macrophages are highly phagocytic and inflammatory, whereas those arising from microglia demonstrate an unexpected signature of globally suppressed cellular metabolism at disease onset. Distinguishing tissue-resident macrophages from infiltrating monocytes will point toward new strategies to treat disease and promote repair in diverse inflammatory pathologies in varied organs.

| S-EPMC4113947 | biostudies-literature

Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system.

Project description:Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKC?. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ER?, ER?, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models.

| S-EPMC4995517 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data