Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 41

Publication Record

Connections

Genetic association signal near NTN4 in Tourette syndrome.
Paschou P, Yu D, Gerber G, Evans P, Tsetsos F, Davis LK, Karagiannidis I, Chaponis J, Gamazon E, Mueller-Vahl K, Stuhrmann M, Schloegelhofer M, Stamenkovic M, Hebebrand J, Noethen M, Nagy P, Barta C, Tarnok Z, Rizzo R, Depienne C, Worbe Y, Hartmann A, Cath DC, Budman CL, Sandor P, Barr C, Wolanczyk T, Singer H, Chou IC, Grados M, Posthuma D, Rouleau GA, Aschauer H, Freimer NB, Pauls DL, Cox NJ, Mathews CA, Scharf JM
(2014) Ann Neurol 76: 310-5
MeSH Terms: Adult, Case-Control Studies, Genome-Wide Association Study, Humans, Nerve Growth Factors, Netrins, Polymorphism, Single Nucleotide, Tourette Syndrome
Show Abstract · Added February 22, 2016
Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10(-3) ) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry-matched controls. Only rs2060546 on chromosome 12q22 (p = 3.3 × 10(-4) ) remained significant after Bonferroni correction. Meta-analysis with the original GWAS yielded the strongest association to date (p = 5.8 × 10(-7) ). Although its functional significance is unclear, rs2060546 lies closest to NTN4, an axon guidance molecule expressed in developing striatum. Risk score analysis significantly predicted case-control status (p = 0.042), suggesting that many of these variants are true TS risk alleles.
© 2014 American Neurological Association.
0 Communities
2 Members
0 Resources
8 MeSH Terms
Neurotrophic factors. Preface.
Lewin GR, Carter BD
(2014) Handb Exp Pharmacol 220: v-vi
MeSH Terms: Animals, Humans, Nerve Growth Factors
Added February 20, 2016
0 Communities
1 Members
0 Resources
3 MeSH Terms
p75 neurotrophin receptor cleavage by α- and γ-secretases is required for neurotrophin-mediated proliferation of brain tumor-initiating cells.
Forsyth PA, Krishna N, Lawn S, Valadez JG, Qu X, Fenstermacher DA, Fournier M, Potthast L, Chinnaiyan P, Gibney GT, Zeinieh M, Barker PA, Carter BD, Cooper MK, Kenchappa RS
(2014) J Biol Chem 289: 8067-85
MeSH Terms: Amyloid Precursor Protein Secretases, Brain, Brain Neoplasms, Cell Line, Tumor, Cell Proliferation, Gene Knockdown Techniques, Glioma, Humans, Mutation, Neoplastic Stem Cells, Nerve Growth Factors, Receptor, Nerve Growth Factor
Show Abstract · Added March 17, 2014
Malignant gliomas are highly invasive, proliferative, and resistant to treatment. Previously, we have shown that p75 neurotrophin receptor (p75NTR) is a novel mediator of invasion of human glioma cells. However, the role of p75NTR in glioma proliferation is unknown. Here we used brain tumor-initiating cells (BTICs) and show that BTICs express neurotrophin receptors (p75NTR, TrkA, TrkB, and TrkC) and their ligands (NGF, brain-derived neurotrophic factor, and neurotrophin 3) and secrete NGF. Down-regulation of p75NTR significantly decreased proliferation of BTICs. Conversely, exogenouous NGF stimulated BTIC proliferation through α- and γ-secretase-mediated p75NTR cleavage and release of its intracellular domain (ICD). In contrast, overexpression of the p75NTR ICD induced proliferation. Interestingly, inhibition of Trk signaling blocked NGF-stimulated BTIC proliferation and p75NTR cleavage, indicating a role of Trk in p75NTR signaling. Further, blocking p75NTR cleavage attenuated Akt activation in BTICs, suggesting role of Akt in p75NTR-mediated proliferation. We also found that p75NTR, α-secretases, and the four subunits of the γ-secretase enzyme were elevated in glioblastoma multiformes patients. Importantly, the ICD of p75NTR was commonly found in malignant glioma patient specimens, suggesting that the receptor is activated and cleaved in patient tumors. These results suggest that p75NTR proteolysis is required for BTIC proliferation and is a novel potential clinical target.
0 Communities
2 Members
0 Resources
12 MeSH Terms
Genetics and diabetic retinopathy.
Schwartz SG, Brantley MA, Flynn HW
(2013) Curr Diabetes Rev 9: 86-92
MeSH Terms: Blindness, Diabetic Retinopathy, Disease Progression, Eye Proteins, Female, Genetic Predisposition to Disease, Glycation End Products, Advanced, Humans, Insulin-Like Growth Factor I, Male, Nerve Growth Factors, Protein Kinase C, Risk Factors, Serpins, Vascular Endothelial Growth Factor A
Show Abstract · Added February 23, 2017
There are many reasons to suspect a genetic influence on the development and progression of diabetic retinopathy, including substantial variability in disease severity among patients with similar risk factors. Linkage studies have suggested associations with chromosomes 1, 3, 12 and others. The most studied individual genes are those encoding vascular endothelial growth factor, aldose reductase, and the receptor for advanced glycation end products, all of which have shown statistically significant associations in multiple series from various parts of the world. At this time, no definite genetic associations with diabetic retinopathy have been consistently reported. This may be due to small sample sizes, differences in study design, underlying genetic differences between study populations, or other factors. As we continue to collect data, these relationships may become more clear.
0 Communities
1 Members
0 Resources
15 MeSH Terms
The SSRI citalopram affects fetal thalamic axon responsiveness to netrin-1 in vitro independently of SERT antagonism.
Bonnin A, Zhang L, Blakely RD, Levitt P
(2012) Neuropsychopharmacology 37: 1879-84
MeSH Terms: Animals, Axons, Citalopram, Coculture Techniques, Female, Fetus, Male, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, Mice, Transgenic, Nerve Growth Factors, Netrin-1, Paroxetine, Receptors, sigma, Serotonin, Serotonin Plasma Membrane Transport Proteins, Serotonin Uptake Inhibitors, Thalamus, Tumor Suppressor Proteins
Show Abstract · Added July 10, 2013
Serotonin (5-hydroxytryptamine, 5-HT) signaling is thought to modulate nervous system development. Genetic and pharmacological studies support the idea that altered 5-HT signaling during development can have enduring consequences on brain function and behavior. Recently, we discovered that 5-HT can modulate thalamic axon guidance in vitro and in vivo. Embryonic thalamic axons transiently express the 5-HT transporter (SERT; Slc6a4) and accumulate 5-HT, suggesting that the SERT activity of these axons may regulate 5-HT-modulated guidance cues. We tested whether pharmacologically blocking SERT using selective 5-HT reuptake inhibitors (SSRIs) would impact the action of 5-HT on thalamic axon responses to netrin-1 in vitro. Surprisingly, we observed that two high-affinity SSRIs, racemic citalopram ((RS)-CIT) and paroxetine, affect the outgrowth of embryonic thalamic axons, but differ with respect to their dependence on SERT blockade. Using a recently developed 'citalopram insensitive' transgenic mouse line and in vitro pharmacology, we show that the effect of (RS)-CIT effect is SERT independent, but rather arises from R-CIT activation of the orphan sigma-1 receptor(σ1, Oprs1). Our results reveal a novel σ1 activity in modulating axon guidance and a 5-HT independent action of a widely prescribed SSRI. By extension, (RS)-CIT and possibly other structurally similar SSRIs may have other off-target actions that can impact neural development and contribute to therapeutic efficacy or side effects.
2 Communities
1 Members
0 Resources
20 MeSH Terms
Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats.
Stankiewicz P, Kulkarni S, Dharmadhikari AV, Sampath S, Bhatt SS, Shaikh TH, Xia Z, Pursley AN, Cooper ML, Shinawi M, Paciorkowski AR, Grange DK, Noetzel MJ, Saunders S, Simons P, Summar M, Lee B, Scaglia F, Fellmann F, Martinet D, Beckmann JS, Asamoah A, Platky K, Sparks S, Martin AS, Madan-Khetarpal S, Hoover J, Medne L, Bonnemann CG, Moeschler JB, Vallee SE, Parikh S, Irwin P, Dalzell VP, Smith WE, Banks VC, Flannery DB, Lovell CM, Bellus GA, Golden-Grant K, Gorski JL, Kussmann JL, McGregor TL, Hamid R, Pfotenhauer J, Ballif BC, Shaw CA, Kang SH, Bacino CA, Patel A, Rosenfeld JA, Cheung SW, Shaffer LG
(2012) Hum Mutat 33: 165-79
MeSH Terms: Abnormalities, Multiple, Child, Child, Preschool, Chromosome Aberrations, Chromosome Mapping, Chromosomes, Human, Pair 10, DNA Copy Number Variations, Developmental Disabilities, Female, Genetic Variation, Homologous Recombination, Humans, In Situ Hybridization, Fluorescence, Infant, Intellectual Disability, Male, Nerve Growth Factors, Oligonucleotide Array Sequence Analysis, Penetrance, Segmental Duplications, Genomic, Sequence Deletion, Vesicular Acetylcholine Transport Proteins
Show Abstract · Added March 27, 2014
We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals. We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers.
© 2011 Wiley Periodicals, Inc.
0 Communities
1 Members
0 Resources
22 MeSH Terms
Structural basis for ligand recognition and activation of RAGE.
Koch M, Chitayat S, Dattilo BM, Schiefner A, Diez J, Chazin WJ, Fritz G
(2010) Structure 18: 1342-52
MeSH Terms: Amino Acid Sequence, Animals, Binding Sites, Crystallography, X-Ray, Humans, Hydrogen-Ion Concentration, Kinetics, Ligands, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Nerve Growth Factors, Protein Binding, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Receptor for Advanced Glycation End Products, Receptors, Immunologic, S100 Calcium Binding Protein beta Subunit, S100 Proteins, Sequence Homology, Amino Acid
Show Abstract · Added March 12, 2014
The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor involved in inflammatory processes and is associated with diabetic complications, tumor outgrowth, and neurodegenerative disorders. RAGE induces cellular signaling events upon binding of a variety of ligands, such as glycated proteins, amyloid-β, HMGB1, and S100 proteins. The X-ray crystal structure of the VC1 ligand-binding region of the human RAGE ectodomain was determined at 1.85 Å resolution. The VC1 ligand-binding surface was mapped onto the structure from titrations with S100B monitored by heteronuclear NMR spectroscopy. These NMR chemical shift perturbations were used as input for restrained docking calculations to generate a model for the VC1-S100B complex. Together, the arrangement of VC1 molecules in the crystal and complementary biochemical studies suggest a role for self-association in RAGE function. Our results enhance understanding of the functional outcomes of S100 protein binding to RAGE and provide insight into mechanistic models for how the receptor is activated.
Copyright © 2010 Elsevier Ltd. All rights reserved.
0 Communities
1 Members
0 Resources
21 MeSH Terms
Ligand-independent signaling by disulfide-crosslinked dimers of the p75 neurotrophin receptor.
Vilar M, Charalampopoulos I, Kenchappa RS, Reversi A, Klos-Applequist JM, Karaca E, Simi A, Spuch C, Choi S, Friedman WJ, Ericson J, Schiavo G, Carter BD, Ibáñez CF
(2009) J Cell Sci 122: 3351-7
MeSH Terms: Amino Acid Sequence, Animals, Axons, COS Cells, Caspase 3, Cell Death, Cercopithecus aethiops, Cross-Linking Reagents, Disulfides, Humans, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Ligands, Molecular Sequence Data, Mutant Proteins, NF-kappa B, Nerve Growth Factors, Protein Multimerization, Protein Transport, Rats, Receptor, Nerve Growth Factor, Receptor-Interacting Protein Serine-Threonine Kinase 2, Signal Transduction, TNF Receptor-Associated Factor 6
Show Abstract · Added March 5, 2014
Dimerization is recognized as a crucial step in the activation of many plasma membrane receptors. However, a growing number of receptors pre-exist as dimers in the absence of ligand, indicating that, although necessary, dimerization is not always sufficient for signaling. The p75 neurotrophin receptor (p75(NTR)) forms disulfide-linked dimers at the cell surface independently of ligand binding through Cys257 in its transmembrane domain. Here, we show that crosslinking of p75(NTR) dimers by cysteine-scanning mutagenesis results in constitutive, ligand-independent activity in several pathways that are normally engaged upon neurotrophin stimulation of native receptors. The activity profiles of different disulfide-crosslinked p75(NTR) mutants were similar but not identical, suggesting that different configurations of p75(NTR) dimers might be endowed with different functions. Interestingly, crosslinked p75(NTR) mutants did not mimic the effects of the myelin inhibitors Nogo or MAG, suggesting the existence of ligand-specific activation mechanisms. Together, these results support a conformational model of p75(NTR) activation by neurotrophins, and reveal a genetic approach to generate gain-of-function receptor variants with distinct functional profiles.
0 Communities
1 Members
0 Resources
24 MeSH Terms
Axon growth-stimulus package includes local translation.
Macara IG, Iioka H, Mili S
(2009) Nat Cell Biol 11: 919-21
MeSH Terms: Animals, Axons, Carrier Proteins, Cells, Cultured, Gene Expression, Models, Biological, Nerve Growth Factor, Nerve Growth Factors, Netrin-1, Neurons, Protein Binding, Protein Biosynthesis, Protein Kinase C, Rats, Signal Transduction, Tumor Suppressor Proteins
Show Abstract · Added March 5, 2014
Translation of localized mRNAs is an important mechanism for controlling spatially discrete cellular processes. The polarity protein Par-3 is locally translated in axons in response to factors such as NGF and netrin-1, and this increased expression is necessary for factor-stimulated axonal outgrowth.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Aggressiveness of HNSCC tumors depends on expression levels of cortactin, a gene in the 11q13 amplicon.
Clark ES, Brown B, Whigham AS, Kochaishvili A, Yarbrough WG, Weaver AM
(2009) Oncogene 28: 431-44
MeSH Terms: Animals, Apoptosis, Autocrine Communication, Carcinoma, Squamous Cell, Cell Proliferation, Chromosomes, Human, Pair 11, Coculture Techniques, Cortactin, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, Humans, Mice, Mice, Nude, Neoplasm Invasiveness, Nerve Growth Factors, RNA, Small Interfering, Rats, Trachea, Tumor Cells, Cultured
Show Abstract · Added March 5, 2014
11q13 amplification is a late-stage event in several cancers that is often associated with poor prognosis. Among 11q13-amplified genes, the actin assembly protein cortactin/CTTN is considered a likely candidate for direct involvement in tumor progression because of its cell motility-enhancing functions. We modulated cortactin expression in head and neck squamous cell carcinoma (HNSCC) cell lines. Cortactin expression levels directly correlated with tumor size, vascularization and cell proliferation in an orthotopic HNSCC in vivo model. In contrast, under normal in vitro culture conditions, cortactin expression levels had no effect on cell proliferation. However, cell lines in which cortactin expression was reduced by knockdown (KD) grew poorly in vitro under harsh conditions of growth factor deprivation, anchorage independence and space constraint. In contrast, overexpression of cortactin enhanced in vitro growth under the same harsh conditions. Surprisingly, defects in growth factor-independent proliferation of cortactin-KD cells were rescued by coculture with cortactin-expressing cells. As the cocultured cells are separated by permeable filters, cortactin-expressing cells must secrete growth-supporting autocrine factors to rescue the cortactin-KD cells. Overall, cortactin expression modulates multiple cellular traits that may allow survival in a tumor environment, suggesting that the frequent overexpression of cortactin in tumors is not an epiphenomenon but rather promotes tumor aggressiveness.
1 Communities
1 Members
0 Resources
19 MeSH Terms