Disease relevance of Ncam1

• We expressed both cytoplasmic domains, as well as cytoplasmic fragments of NCAM, as fusion proteins in Escherichia coli and used them for ligand affinity chromatography or glutathione S-transferase (GST) pull-down assays [1].
• We describe a method of generating an enriched population of NCAM-positive cells from a human teratocarcinoma cell line (NTera2/D1) and their differentiation into midbrain dopaminergic neurons in the absence of the caudalizing factor retinoic acid (RA) [2].
• Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas [3].
• The expression of NCAM and cadherin isoforms in the glucagonoma suggest that this transformed alpha-cell type has converted to an immature phenotype with strong neuronal traits, reflecting the early palce of glucagon-producing cells in the islet cell lineage [3].
• The cell adhesion molecules integrin and Neural cell adhesion molecule (NCAM) play important roles in neurite outgrowth and fasciculation [4].

Psychiatry related information on Ncam1

• Integrin alphav and NCAM mediate the effects of GDNF on DA neuron survival, outgrowth, DA turnover and motor activity in rats [4].
• Here, we show that intracerebroventricular administration of the FG loop (FGL), a synthetic 15 amino acid peptide corresponding to the binding site of NCAM for the fibroblast growth factor receptor 1 (FGFR1), immediately after training rats in fear conditioning or water maze learning, induced a long-lasting improvement of memory [5].
• Here, we questioned whether training-induced modulation of PSA-NCAM expression might be related to individual differences in spatial learning abilities [6].
• Present findings indicate that exposure to ethanol induces learning and memory deficits probably by generating reactive oxygen species and downregulating NCAM 180 in hippocampus of aged rats [7].
• Pentyl-4-yn-valproic acid enhances both spatial and avoidance learning, and attenuates age-related NCAM-mediated neuroplastic decline within the rat medial temporal lobe [8].

High impact information on Ncam1

• Hippocampal long-term potentiation and neural cell adhesion molecules L1 and NCAM [9].
• L1 and NCAM mediate cell interactions during neural development and are strongly expressed in the hippocampus [9].
• Here we investigate the role of the neural cell adhesion molecules L1 and NCAM in hippocampal long-term potentiation (LTP), a sustained-use-dependent increase in synaptic efficacy that has been implicated in learning and memory [9].
• The VASE exon downregulates the neurite growth-promoting activity of NCAM 140 [10].
• Alternative splicing generates 20-30 isoforms of NCAM and these can also be differentially glycosylated [10].

Chemical compound and disease context of Ncam1

• Function-blocking anti-integrin alphav and anti-NCAM antibodies antagonized the effects of GDNF on DA neuron survival, outgrowth, DA turnover, and locomotor activity in rats [4].
• Underexpression of neural cell adhesion molecule and neurotrophic factors in rat brain following thromboxane A(2)-induced intrauterine growth retardation [11].
• Thus it was demonstrated for the first time that IUGR newborn rat kidneys express N-CAM and cadherin adhesion molecules at specific sites of the nephron [12].
• The nerve growth factor-inducible large external (NILE) glycoprotein and the neural cell adhesion molecule (N-CAM) have both been implicated in the process of nerve fiber fasciculation [13].
• In order to acquire some insight into potential histogenetically plastic functions of E-NCAM, in another series of experiments adult rats were treated with kainic acid, a powerful excitotoxic and convulsant glutamate analog eliciting status epilepticus [14].

Biological context of Ncam1

• The Neural Cell Adhesion Molecule (NCAM) plays a crucial role in development of the central nervous system regulating cell migration, differentiation and synaptogenesis [15].
• In the present study, we demonstrate that activation of NCAM and L1 can lead to phosphorylation of the FGFR [16].
• Antibodies against the fibronectin type-III homology modules of NCAM, in which a putative site for ATP binding and hydrolysis is located, also abolished the neurite outgrowth-promoting effect of ATP [17].
• Polypeptide variation in an N-CAM extracellular immunoglobulin-like fold is developmentally regulated through alternative splicing [18].
• Transfection of hippocampal neurons of NCAM-deficient mice revealed that of the three major NCAM isoforms only NCAM140 can act as a homophilic receptor that induces neurite outgrowth [19].

Anatomical context of Ncam1

• Here we investigate whether stimulation of neurite outgrowth by this synthetic ligand of NCAM involves FGFRs [20].
• In vitro, NCAM-NCAM binding has been shown to induce neurite outgrowth, presumably through an activation of fibroblast growth factor receptors (FGFRs) [20].
• Comparative expression patterns of T-, N-, E-cadherins, beta-catenin, and polysialic acid neural cell adhesion molecule in rat cochlea during development: implications for the nature of Kölliker's organ [21].
• The expression and distribution of neural cell adhesion molecule (NCAM), cadherins and beta-catenin were investigated in the CG-4 cell line and primary rat oligodendrocyte progenitor cells (O-2A) by immunofluorescence and Western blotting [22].
• Rat oligodendrocyte O-2A precursor cells and the CG-4 oligodendrocyte precursor cell line express cadherins, beta-catenin and the neural cell adhesion molecule, NCAM [22].

Associations of Ncam1 with chemical compounds

• We have recently identified a neuritogenic ligand, termed the C3 peptide, of the first immunoglobulin (lg) module of NCAM using a combinatorial library of synthetic peptides [20].
• Immunostaining results demonstrated the wide distribution of integrin alphav and NCAM in all mesencephalic neurons [4].
• These results demonstrate that integrin alphav and NCAM mediate the effects of GDNF on DA neuron survival and outgrowth during development and on DA turnover and motor function during adulthood [4].
• Extracellular adenosine triphosphate affects neural cell adhesion molecule (NCAM)-mediated cell adhesion and neurite outgrowth [17].
• On postnatal day 2, NCAM expression was decreased in rat cerebral cortex, and reelin expression was decreased in hippocampus from levels in controls without maternal thromboxane exposure [11].

Physical interactions of Ncam1

• Here we show that FGL, a neural cell adhesion molecule (NCAM)-derived peptide binding to and inducing phosphorylation of the fibroblast growth factor receptor (FGFR), acts neuroprotectively after an ischemic insult both in vitro and in vivo [23].
• Together, these findings indicate that homophilic N-CAM binding leads to inhibition of astrocyte proliferation via a pathway involving the glucocorticoid receptor and that the ability of N-CAM to influence astrocyte proliferation and neurite outgrowth involves different signal pathways [24].

Regulatory relationships of Ncam1

• A peptide from the first fibronectin domain of NCAM acts as an inverse agonist and stimulates FGF receptor activation, neurite outgrowth and survival [25].
• Growth factors, eg, transforming growth factor-beta1, down-regulated I-CAM-1- and V-CAM-1-coding mRNAs and stimulated N-CAM expression of HSC [26].
• NMDA receptor and nitric oxide synthase activation regulate polysialylated neural cell adhesion molecule expression in adult brainstem synapses [27].
• Addition of N-CAM inhibited MAP kinase activity induced by basic fibroblast growth factor in astrocytes [24].
• A rat brain Golgi sialyltransferase activity capable of the differentiation-dependent control of N-CAM sialylation state is described [28].

Other interactions of Ncam1

• An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons [15].
• Furthermore, we were able to show that binding of these novel binding proteins, as well as the previously described interaction partners ROK alpha (rho A binding kinase alpha) and alpha- and beta-tubulin, bind to specific cytosolic sequences of NCAM [1].
• These results collectively indicate that NCAM and tPA reciprocally act as important regulators in the modulation of synaptic plasticity via a Ras-MAPK-involved signaling pathway [29].
• Whereas primary islet cells at all ages express unsialylated NCAM and E-cadherin, as do insulinomas, the glucagonomas express the polysialylated NCAM, which is characteristic for developing neurons [3].
• No significant differences in NCAM expression were seen in hippocampus, nor did reelin expression differ in cerebral cortex between control and IUGR groups [11].

Analytical, diagnostic and therapeutic context of Ncam1

• We investigated expression patterns of neural cell adhesion molecule (NCAM) and reelin in this model by semiquantitative competitive polymerase chain reactions [11].
• However, the number of tubules expressing N-CAM and pan-cadherin was increased in the IUGR group compared with the control group [12].
• We demonstrate by means of confocal microscopy that cultured magnocellular VP and OT neurons express strong immunoreactivity for PSA-NCAM [30].
• The most intense NCAM PSA immunoreactivity was observed in the medial and triangular septal nuclei, regions that regulate hippocampal theta rhythm during memory consolidation [31].
• We show that enzymatic removal of PSA with endoneuraminidase-N (endo-N) abolished preferential formation of synapses on NCAM-expressing cells in heterogenotypic cocultures of wild-type and NCAM-deficient hippocampal neurons [32].

References