Selected differentially expressed genes in BA44 to BA47 (ANO......
Selected differentially expressed genes in BA44 to BA47 (ANOVA and t-test P < 0.01, fold change 1.3t)More...
Positive relationships between GRIN2A and other components at different levels (count: 1)
Genetic/epigenetic locus
Protein and other molecule
Cell and molecular pathway
Neural system
Cognition and behavior
Symptoms and signs
Environment
Positive relationship network of GRIN2A in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network.
If the mapped gene or protein is not from literature, square node would be used instead of Circle node.
Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node.
Right-click will show also the menus to link to the report page of the node and remove the node and related edges.
Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web
Negative relationships between GRIN2A and MDD (count: 0)
Negative relationships between GRIN2A and other components at different levels (count: 0)
Ca2+ that enters the cell from the outside is a principal so......
Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it. The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM).More...
Amyotrophic lateral sclerosis (ALS) is a progressive, lethal......
Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, degenerative disorder of motor neurons. The hallmark of this disease is the selective death of motor neurons in the brain and spinal cord, leading to paralysis of voluntary muscles. Mutant superoxide dismutase 1 (SOD1), as seen in some familial amyotrophic lateral sclerosis (FALS) cases, may be toxic because it is unstable, forming aggregates in the motor neuron cytoplasm, axoplasm and mitochondria. Within mitochondria, mutant SOD1 may interfere with the anti-apoptotic function of Bcl-2, affect mitochondrial import by interfering with the translocation machinery (TOM/TIM), and generate toxic free radicals (ROS) via aberrant superoxide chemistry. These changes may then result in abnormal mitochondrial energy metabolism, Ca2+ handling, and release of pro-apoptotic factors. Reactive oxygen species (ROS), produced within mitochondria, inhibit the function of EAAT2, the main glial glutamate transporter protein, responsible for most of the reuptake of synaptically released glutamate. Glutamate excess causes neurotoxicity by increasing intracellular calcium, which enhances oxidative stress and mitochondrial damage. Mutant SOD1 can also trigger oxidative reactions by various means including by increasing levels of peroxynitrite, which can then cause damage through the formation of hydroxyl radicals or via nitration of tyrosine residues on proteins. Nitration may target neurofilament proteins, disrupting their phosphorylation and affecting axonal transport. Collectively, these mechanisms (or a combination thereof) are predicted to disturb cellular homeostasis (within glial and/or motor neurons), ultimately triggering motor neuron death.More...
Alzheimer's disease (AD) is a chronic disorder that slowly d......
Alzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. The extracellular Abeta oligomers may activate caspases through activation of cell surface death receptors. Alternatively, intracellular Abeta may contribute to pathology by facilitating tau hyper-phosphorylation, disrupting mitochondria function, and triggering calcium dysfunction. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specifically the more amyloidogenic form, Abeta42. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress.More...
Systemic lupus erythematosus (SLE) is characterized by circu......
Systemic lupus erythematosus (SLE) is characterized by circulating IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and certain cytoplasmic components. Immune complexes comprising autoantibody and self-antigen is deposited particulary in the renal glomeruli and mediate a systemic inflammatory response by activating complement or via Fc-gamma-R-mediated neutrophil and macrophage activation. Activation of complement leads to injury both through formation of the membrane attack complex (C5b-9) or by generation of the anaphylatoxin and cell activator C5a. Neutrophils and macrophages cause tissue injury by the release of oxidants and proteases.More...
Hippocampal long-term potentiation (LTP), a long-lasting inc......
Hippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippocampus induces glutamate release and activation of glutamate receptors in dendritic spines. A large increase in i resulting from influx through NMDA receptors leads to constitutive activation of CaM kinase II (CaM KII). Constitutively active CaM kinase II phosphorylates AMPA receptors, resulting in potentiation of the ionic conductance of AMPA receptors. Early-phase LTP (E-LTP) expression is due, in part, to this phosphorylation of the AMPA receptor. It is hypothesized that postsynaptic Ca2+ increases generated through NMDA receptors activate several signal transduction pathways including the Erk/MAP kinase and cAMP regulatory pathways. The convergence of these pathways at the level of the CREB/CRE transcriptional pathway may increase expression of a family of genes required for late-phase LTP (L-LTP).More...
Glutamatergic-mediated nitric oxide (NO) production occurs v......
Glutamatergic-mediated nitric oxide (NO) production occurs via the N-methyl-D-aspartic acid (NMDA) postsynaptic density protein 95 (PSD95)-neuronal nitric oxide synthase (NOS1) ternary complex. The increased intracellular Ca2+ stimulates the interaction of nNOS and calmodulin (CaM) and the translocaton of nNOS from the plasma membrane to the cytoplasm. The dephosphorylation of nNOS by Calcineurin catalyzes the conversion of arginine to citrulline and nitric oxide (NO), which turns on guanylate cyclase and the various cGMP regulated signaling pathways.More...
Ca2+ signal generated through NMDA receptor in the post-syna......
Ca2+ signal generated through NMDA receptor in the post-synaptic neuron activates adenylate cyclase signal transduction, leading to the activation of PKA and phosphorylation and activation of CREB-induced transcription. The isoforms of adenylate cyclase that are activated by Ca2+ in the brain are I, III and IX.More...
NMDA receptors are a subtype of ionotropic glutamate recepto......
NMDA receptors are a subtype of ionotropic glutamate receptors that are specifically activated by a glutamate agonist N-methyl-D-aspartate (NMDA). Activation of NMDA receptor involves opening of the ion channel that allows the influx of Ca2+. NMDA receptors are central to activity dependent changes in synaptic strength and are predominantly involved in the synaptic plasticity that pertain to learning and memory. A unique feature of NMDA receptor unlike other glutamate receptors is the requirement of dual activation of the NMDA receptor, which require both voltage dependent and ligand dependent activation. At resting membrane potential the NMDA receptors are blocked by Mg2+. The voltage dependent Mg2+ block is relieved upon depolarization of the post-synpatic membrane. The ligand dependent activation of the NMDA receptor requires co-activation by two ligands, namely glutamate and glycine. NMDA receptors are coincidence detector, and are activated only if there is simultaneous activation of both pre and post-synaptic cell. Upon activation NMDA receptors allow the influx of Ca2+ that initiates various molecular signaling cascades that are involved in the process of learning and memory.More...
Ca2+ influx through the NMDA receptor initiates subsequent m......
Ca2+ influx through the NMDA receptor initiates subsequent molecular pathways that have a defined role in establishing long-lasting synaptic changes. The molecular signaling initiated by a rise in Ca2+ within the spine leads to phosphorylation of Cyclic AMP Response Element binding protein (CREB) at serine 133 which is involved in the transcription of genes that results in long lasting changes in the synapse. The phosphorylation of CREB by increased Ca2+ can be brought about by distinct molecular pathways that may involve MAP kinase, activation of adenylate cyclase, activation of CaMKII and/or the activation of CaMKIV.More...
Chemical synapses are specialized junctions that are used fo......
Chemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron, muscle cell or glad cell. The pre and the post-synaptic cell are separated by a gap of 20nm called the synaptic cleft. The signals pass in a unidirection from pre-synaptic to post-synaptic. The pre-synaptic neuron communicates via the release of neurotransmitter which bind the receptors on the post-synaptic cell.More...
Ca2+ influx through the NMDA receptor initiates subsequent m......
Ca2+ influx through the NMDA receptor initiates subsequent molecular pathways that have a defined role in establishing long-lasting synaptic changes. The molecular signaling initiated by a rise in Ca2+ within the spine leads to phosphorylation of Cyclic AMP Response Element binding protein (CREB) at serine 133 which is involved in the transcription of genes that results in long lasting changes in the synapse. The phosphorylation of CREB by increased Ca2+ can be brought about by distinct molecular pathways that may involve MAP kinase, activation of adenylate cyclase, activation of CaMKII and/or the activation of CaMKIV.More...
The neurotransmitter in the synaptic cleft released by the p......
The neurotransmitter in the synaptic cleft released by the pre-synaptic neuron binds specific receptors located on the post-synaptic terminal. These receptors are either ion channels or G protein coupled receptors that function to transmit the signals from the post-synaptic membrane to the cell body.More...
Ca2+ influx through the NMDA receptor leads to the activatio......
Ca2+ influx through the NMDA receptor leads to the activation of Ras kinase via the activation of RasGRF.More...
GRIN2A related interactors from protein-protein interaction data in HPRD (count: 25)
Basic Information
Positive relationships between GRIN2A and other components at different levels (count: 1)
