Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mental retardation, hydrocephalus, and agenesis of the corpus callosum are observed both in fetal alcohol syndrome (FAS) and in children with mutations in the gene for the cell adhesion molecule L1. We studied the effects of ethanol on cell-cell adhesion in mouse fibroblasts transfected with human L1. L1-transfected fibroblasts exhibited increased cell-cell adhesion compared with wild-type or vector-transfected controls. Ethanol potently and completely inhibited L1-mediated adhesion both in transfected L cells and NIH/3T3 cells. Half-maximal inhibition was observed at 7 mM ethanol, a concentration achieved in blood and brain after ingesting one alcoholic beverage. In contrast, ethanol did not inhibit the adhesion of fibroblasts transfected with vector alone or with N-CAM-140. L1-mediated cell-cell adhesion was inhibited with increasing potency by n-propanol and n-butanol, but was not inhibited at all by n-alcohols of 5 to 8 carbons, acetaldehyde, or acetate, suggesting that ethanol interacts directly with a small hydrophobic pocket within L1. Phenylalanine, teratogenic anticonvulsants, and high concentrations of glucose did not inhibit L1-mediated cell-cell adhesion. Ethanol also inhibited potently the heterotypic adhesion of rat cerebellar granule cells to a monolayer of L1-transfected NIH/3T3 cells, but had no effect on their adhesion to N-CAM-140 or vector-transfected NIH/3T3 cells. Because L1 plays a role in both neural development and learning, ethanol inhibition of L1-mediated cell-cell interactions could contribute to FAS and ethanol-associated memory disorders.
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PMID:Alcohol inhibits cell-cell adhesion mediated by human L1. 860 70

Cortical malformations such as cortical dysplasia and heterotopia constitute the underlying pathology of epilepsy and mental retardation. It is thus important to elucidate the pathogenesis of these migration disorders from the neuropathological viewpoint based upon animal experiments. In this review, I describe the experiment in which low-dose prenatal X-or gamma-irradiation was performed at the mid-gestational period of mice or rats. Low-dose irradiation as low as 150 mGy induced decelerated migration of cortical neurons during the embryonic period together with a changed pattern of cell adhesion molecule, N-CAM. In addition, the effect of radiation remained at least up until 3-week postnatal as disorganized neuronal allocation with respect to the birthdate. With time of further maturation in the neocortex, however, the architecture, in terms of the pattern of distribution of the labeled neurons, returned closely to that found in non-irradiated control animals. Considering the fact that the number of labeled cells per unit cortical area decreased considerably from 3-week to 8-week postnatal, it is conceivable that apoptotic cell death might have occurred in aberrantly placed neurons. Recent progress of molecular genetical approach to human hereditary neurodevelopmental diseases is briefly reviewed, since it greatly contributes to our understanding on the pathogenesis of neuronal migration disorders.
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PMID:[Pathogenesis of the neuronal migration disorder, with special reference to the animal model of prenatal exposure to low-dose ionizing radiation]. 907 Nov 86

Neural cell adhesion molecules (CAMs) of the immunoglobulin superfamily nucleate and maintain groups of cells at key sites during early development and in the adult. In addition to their adhesive properties, binding of CAMs can affect intracellular signaling. Their ability to influence developmental events, including cell migration, proliferation, and differentiation can therefore result both from their adhesive as well as their signaling properties. This review focuses on the two CAMs for which the most information is known, the neural CAM, N-CAM, and L1. N-CAM was the first CAM to be characterized and, therefore, has been studied extensively. The binding of N-CAM to cells leads to a number of signaling events, some of which result in changes in gene expression. Interest in L1 derives from the fact that mutations in its gene lead to human genetic diseases including mental retardation. Much is known about modifications of the L1 cytoplasmic domain and its interaction with cytoskeletal molecules. The study of CAM signaling mechanisms has been assay-dependent rather than molecule-dependent, with particular emphasis on assays of neurite outgrowth and gene expression, an emphasis that is maintained throughout the review. The signals generated following CAM binding that lead to alterations in cell morphology and gene expression have been linked directly in only a few cases. We also review information on other CAMs, giving special consideration to those that are anchored in the membrane by a phospholipid anchor. These proteins, including a form of N-CAM, are presumed to be localized in lipid rafts, membrane substructures that include distinctive subsets of cytoplasmic signaling molecules such as members of the src-family of nonreceptor protein tyrosine kinases. In the end, these studies may reveal that what CAMs do after they bind cells together may have as profound consequences for the cells as the adhesive interactions themselves. This area will therefore remain a rich ground for future studies.
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PMID:Cellular signaling by neural cell adhesion molecules of the immunoglobulin superfamily. 1084 56