Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene encoding the D2 dopamine receptor (DRD2) is located on human chromosome 11q23 and has been circumstantially associated with a number of human disorders including Parkinson's disease, schizophrenia, and susceptibility to alcoholism. To determine the physical structure of the DRD2 gene, we utilized cosmid cloning, isolation of yeast artificial chromosomes (YACs), and pulsed-field gel electrophoresis to construct a long-range physical map of human chromosome 11q23 linking the genes for the DRD2 and neural cell adhesion molecule (NCAM). The D2 dopamine receptor gene extends over 270 kb and includes an intron of approximately 250 kb separating the putative first exon from the exons encoding the receptor protein. The resulting physical map spans more than 1.5 mb of chromosome band 11q23 and links the DRD2 gene with the gene encoding the NCAM located 150 kb 3' of the DRD2 gene and transcribed from the same DNA strand. We additionally located the sites of at least four hypomethylated HTF islands within the physical map, which potentially indicate the sites of additional genes. High-resolution fluorescent in situ suppression hybridization using cosmid and YAC clones localized this gene cluster between the ApoAI and STMY loci at the interface of bands 11q22.3 and 11q23.1.
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PMID:Structure and linkage of the D2 dopamine receptor and neural cell adhesion molecule genes on human chromosome 11q23. 147 42

The level of a neural cell adhesion molecule (NCAM) serum fragment in autism was determined by using an antiserum prepared with immunoaffinity purified mouse NCAM. Autistic patients (N = 16) had statistically significantly decreased serum NCAM levels compared with age-matched controls (p less than 0.0005). This observation could not be attributed to a medication-induced effect. Depressed serum NCAM levels in autism are distinct from schizophrenia, in which serum NCAM levels are elevated.
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PMID:Expression of a neural cell adhesion molecule serum fragment is depressed in autism. 213 94

The expression of a 70-kD serum fragment of the neural cell adhesion molecule (N-CAM) in schizophrenia is described. Schizophrenic patients (n = 40) were found to have statistically significant increases (p less than 0.0001) in serum N-CAM levels when compared to normal individuals (n = 26), and this could not be associated with age or sex. This difference was more marked (p less than 0.0001) between type II schizophrenics (n = 13) and normal individuals (n = 26) than when patients in the overlap group between type I and type II schizophrenia (n = 18) were compared to normal individuals (p less than 0.001). This difference remained significant (p less than 0.01) when overlap patients were compared to those of type II schizophrenia. Furthermore, schizophrenic patients with lower serum N-CAM proved to be better responders to neuroleptic therapy. We suggest that these elevated serum N-CAM levels reflect an increased synaptic turnover rate in this psychotic state.
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PMID:The expression of an N-CAM serum fragment is positively correlated with severity of negative features in type II schizophrenia. 336 55

The regulated expression of neural cell adhesion molecule (NCAM) isoforms in the brain is critical for many neurodevelopmental processes including neurulation, axonal outgrowth, and the establishment of neuronal connectivity. We have investigated the expression of the major adult isoforms of NCAM (NCAM-180, NCAM-140, and NCAM-120) and its embryonic highly polysialylated isoform (PSA-NCAM) in the hippocampal region of postmortem brains from 10 schizophrenic and 11 control individuals. Immunohistochemical analysis with a monoclonal antibody recognizing the PSA-NCAM revealed immunoreactivity primarily in the dentate gyrus and in a subset of cells in the hilus region. We have observed a 20-95% reduction in the number of hilar PSA-NCAM-immunoreactive cells in the great majority of schizophrenic brains. The change in PSA-NCAM immunoreactivity is not obvious in other hippocampal subfields. Western blots of tissues from the hippocampal region (as well as from the frontal cortex) probed with a polyclonal antibody recognizing all NCAM isoforms did not reveal significant changes in the overall expression of NCAM, suggesting that the decrease in PSA-NCAM-immunoreactive cells may be related to post-translational processing of the molecule. The expression of this embryonic form of NCAM has been proposed to be related to synaptic rearrangement and plasticity. Therefore, the decrease in PSA-NCAM immunoreactivity in schizophrenic hippocampi may suggest an altered plasticity of this structure in a large proportion of schizophrenic brains. These findings may bear significance to the "neurodevelopmental hypothesis" of schizophrenia.
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PMID:Decreased expression of the embryonic form of the neural cell adhesion molecule in schizophrenic brains. 770 24

The long arm of chromosome 11 is of interest in schizophrenia research because of three independent reports of balanced 11q translocations cosegregating with schizophrenia and other major psychiatric illness in pedigrees. In addition, a number of candidate genes for psychosis are located in the translocated regions. These include the dopamine D2 receptor, porphobilinogen deaminase, which has shown an allelic association with schizophrenia, and neural cell adhesion molecule, a cell surface glycoprotein involved in neuronal cell-cell recognition during brain development. To search for a schizophrenia locus on chromosome 11q, we conducted linkage analyses in 12 multiplex pedigrees. Sixteen DNA markers, including the above three candidate genes, were used to screen the entire long arm of chromosome 11. None of these markers were supportive of linkage to schizophrenia regardless of whether the affected phenotype was defined narrowly or broadly, whether high or low penetrance was assumed. Both dominant and recessive models tested more than 130 centimorgans of chromosome 11q, and therefore, the reported translocation regions. The results provide no evidence for a susceptibility locus for schizophrenia on chromosome 11q in these pedigrees.
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PMID:A linkage study of chromosome 11q in schizophrenia. 843 42

The addition of poly-alpha2,8-N-acetylneuraminic acid (polysialic acid; PSA) to the neural cell adhesion molecule NCAM plays a crucial role in neural development [1-3], neural regeneration [4], and plastic processes in the vertebrate brain associated with neurite outgrowth [5], axonal pathfinding [6], and learning and memory [7,-9]. PSA levels are decreased in people affected by schizophrenia [10], and PSA has been identified as a specific marker for some neuroendocrine and lymphoblastoid tumours [11-13]; expression of PSA on the surface of these tumour cells modulates their metastatic potential [11-13]. Studies aimed at understanding PSA biosynthesis and the dynamics of its production have largely been promoted by the cloning of polysialyltransferases (PST-1 in hamster; PST in human and mouse) [14-16]. However, the number of enzymes involved in the biosynthesis of PSA has not been identified. Using incompletely glycosylated NCAM variants and soluble recombinant glycosyltransferases, we reconstituted the site at which PST-1 acts to polysialylate NCAM in vitro. The data presented here clearly demonstrate that polysialylation of NCAM is catalyzed by a single enzyme, PST-1, and that terminal sialylation of the N-glycan core is sufficient to generate the PSA acceptor site. Our results also show that PST-1 can act on core structures with the terminal sialic acid connected to galactose via an alpha2,3 or alpha2,6 linkage.
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PMID:Polysialylation of NCAM by a single enzyme. 880 71

Transforming growth factor beta s (TGF beta s) are potent immunosuppressive molecules released in the brain after injury. We hypothesized that TGF beta levels in cerebrospinal fluid (CSF) of schizophrenic patients would be altered because TGF beta can influence neural cell adhesion molecule (N-CAM) expression in vitro. The levels of TGF beta 1 and beta 2 in CSF of patients with schizophrenia and normal controls measured by ELISA showed no differences. There was evidence that the stability of TGF beta in CSF may be altered in schizophrenia. For a limited sample, TGF beta 1 and N-CAM concentrations were significantly correlated in normal patients (r = 0.98) but not in schizophrenics. The results do not support an active neurodegeneration or anti-inflammatory response in the central nervous system, which is reflected in the CSF of chronic schizophrenics.
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PMID:Transforming growth factors beta 1 and beta 2 in the cerebrospinal fluid of chronic schizophrenic patients. 898 92

The neuronal organization and patterns of afferent innervation are abnormal in the cingulate cortex in schizophrenia, and associated changes in synaptic terminals could be present. A panel of monoclonal antibodies was defined with biochemical and fusion protein studies as detecting syntaxin (antibody SP6), synaptophysin (antibody SP4) and synaptosomal-associated protein-25 (antibody SP12). These antibodies and a polyclonal antibody reactive with neural cell adhesion molecule were used to investigate the cingulate cortex in schizophrenia. Immunocytochemistry indicated that syntaxin immunoreactivity had a considerably wider distribution than synaptophysin. Overall, multivariate analysis indicated increased synaptic terminal protein immunoreactivity in schizophrenia compared to controls (P=0.004). Controlled for age and post mortem interval, syntaxin immunoreactivity was significantly elevated in schizophrenia (P=0.004), and neural cell adhesion molecule immunoreactivity was also elevated (P=0.05). The neural cell adhesion molecule to synaptophysin ratio was increased (P=0.005), possibly indicating the presence of less mature synapses in schizophrenia. Elevated syntaxin immunoreactivity is consistent with increased glutamatergic afferents to the cingulate cortex in schizophrenia, and combined with the neural cell adhesion molecule to synaptophysin ratio results suggests that synaptic function in this region in schizophrenia may be abnormal.
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PMID:Cingulate cortex synaptic terminal proteins and neural cell adhesion molecule in schizophrenia. 913 92

The hypothesis of a neurodevelopmental dysfunction being involved in the etiology of schizophrenia is suggested by the observation of morphological alterations in the brains of schizophrenia patients. These alterations may be caused by defects in neural cell differentiation or migration, which could lead to disrupted neuronal circuitry and to the schizophrenia symptomatology. The neural cell adhesion molecule (NCAM) plays a major role in cell migration and axon outgrowth, and is involved in synaptic plasticity mechanisms implicated in adult cognitive functions. Altered levels of the NCAM polysialylated form, PSA-NCAM, in the brain of schizophrenia patients have been reported, and are supportive of a role for this molecule in the disorder. To investigate the possible involvement of the NCAM gene in schizophrenia, we conducted a comprehensive genetic study, which included linkage analysis and an association study employing the Haplotype Relative Risk (HRR) design in nuclear families. Our results indicate that structural alterations in the NCAM gene are unlikely to play a major role in schizophrenia, although a function for the NCAM molecule in the etiology of the disease remains an intriguing hypothesis.
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PMID:NCAM and schizophrenia: genetic studies. 915 19

Schizophrenia is a neuropsychiatric disorder of unknown etiology associated with subtle changes in brain morphology. The cell recognition molecules (CRMs) neural cell adhesion molecule (N-CAM) and L1 are involved in morphoregulatory events and numerous neurodevelopmental processes. We found a selective increase of 105- to 115-kDa N-CAM in the hippocampus and prefrontal cortex of patients with schizophrenia while other N-CAM isoforms and L1 proteins were not altered. There was also evidence for an abnormality in CRM expression in schizophrenic patients: concentrations of 200-kDa L1 were strongly correlated with expression of N-CAM isoforms and cleaved L1 proteins in controls, whereas these correlations were absent in patients with schizophrenia. The increase of the 105- to 115-kDa N-CAM isoform in the brains of patients with schizophrenia confirms previous cerebrospinal fluid findings. Increased N-CAM in schizophrenia may result from structural brain abnormalities, from glial processing of N-CAM, or from an aberration in the regulation of N-CAM expression.
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PMID:Abnormal expression of cell recognition molecules in schizophrenia. 950 Sep 55


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