Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SEZ-12 is one of the seizure-related cDNAs which was isolated by differential hybridization from primary cultured neurons from the mouse cerebral cortex with or without pentylenetetrazol (PTZ). SEZ-12 expression is transiently down-regulated in the mouse brain by injection of PTZ. To characterize SEZ-12, isolation of full-length cDNA and nucleotide sequence analysis were performed. The deduced amino acid sequence of SEZ-12 revealed that it encodes membrane-bound C-type lectin and has a significant homology to that of human cDNA, DGCR2 and IDD, which were cloned from a balanced translocation breakpoint associated with the DiGeorge syndrome. The isolated cDNA was about 4 kb in length and the message was expressed ubiquitously in various organs with low-abundance. Previously, we also cloned a transmembrane protein which is probably involved in cell-cell interaction by the differential hybridization technique. These findings suggest that transmembrane signaling in neuronal cells may have an important role in PTZ-induced seizure.
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PMID:Cloning of SEZ-12 encoding seizure-related and membrane-bound adhesion protein. 863 60

Frequent allelic losses on chromosome 22q in small cell lung carcinomas (SCLCs) and advanced non-small cell lung carcinomas indicate the presence of tumor suppressor gene(s) on this chromosome arm. We detected a homozygous deletion at 22q12.1 in a SCLC cell line, Lu24. Cloning of the breakpoints of the Lu24 deletion revealed that the deletion was interstitial and 428, 131 bp in size. The deleted region contained the SEZ6L (Seizure 6-like) gene, whose structure had been partially determined by the chromosome 22 sequencing project. We determined the full length cDNA sequence for the SEZ6L gene based on the genomic sequence for the SEZ6L locus using the GENSCAN program and the RT - PCR method. The deduced SEZ6L protein was a transmembrane protein of 1024 amino acids with multiple domains involved in protein - protein interaction and signal transduction. SEZ6L expression was detected in a variety of human tissues, including lung, while its expression was detected in 14 (30%) of 46 lung cancer cell lines examined. Missense mutations were detected in three (7%) of the 46 cell lines, and a 1 bp deletion in the polypyrimidine tract preceding exon 4 was detected in one (2%) of 46 primary lung cancers. Therefore, it is possible that genetic and/or epigenetic SEZ6L alterations are involved in the development and/or progression in a subset of lung cancer, although functional analysis of the SEZ6L gene as well as molecular analysis of other genes in the homozygously deleted region is necessary to understand the pathogenetic significance of 22q deletions in human lung carcinogenesis.
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PMID:Identification of a 428-kb homozygously deleted region disrupting the SEZ6L gene at 22q12.1 in a lung cancer cell line. 1117 39

Ank is a 492-amino acid multipass transmembrane protein involved in the regulation of extracellular inorganic pyrophosphate levels and the control of tissue calcification. Previous Northern blot hybridization experiments revealed that Ank mRNA was expressed in the brain, but there have been no reports describing the anatomical sites or specific cell types in the brain that express Ank protein. In this study, we demonstrate that Ank is expressed primarily in human brain neurons, with the highest levels of expression observed in the thalamus, the III and V cortical layers, the Purkinje cells of the cerebellum, clusters of cells in the dorsal portion of the pons and midbrain, and neurons of the anterior horn of the spinal cord. In primary mouse neuronal cell cultures, Ank is detected on both the cell body and on cell extensions, mainly dendrites. In the rat brain, Ank mRNA is expressed at relatively high levels in the thalamus, midbrain, and spinal cord, and the Ank protein expression pattern is similar to that observed in the human brain. Finally, we observed a significant increase in Ank immunoreactivity in the rat amygdala, the CA-2 and CA-3 layers of the hippocampus, and the cerebral cortex after the induction of seizure activity. Ank regulation of ATP and/or inorganic pyrophosphate release from neurons may function to modulate the membrane excitability and cell death associated with seizure activity.
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PMID:Progressive ankylosis (Ank) protein is expressed by neurons and Ank immunohistochemical reactivity is increased by limbic seizures. 1286 Oct 42

We describe the pattern of early childhood seizures within a family with autosomal dominant chondrocalcinosis (CCAL, which causes adult-onset arthritis). All affected family members with CCAL experienced seizures in early childhood, usually, but not always, associated with fever. Similarities exist to the syndrome of generalized epilepsy with febrile seizures plus (GEFS+). A mutation within the ANKH gene on chromosome 5p has been found previously in this family; other patients with familial CCAL (but without seizures) have mutations in the same gene. ANKH codes for a transmembrane protein involved in the regulation of extracellular pyrophosphate ion levels, although its precise mechanism of action remains unclear. It is highly expressed in the brain, and its expression may be influenced by seizure activity. The mutation within this family creates a premature initiation codon, adding four amino acids to the N-terminus of the protein. We postulate that this may lead to a gain of function, causing seizure susceptibility as well as chondrocalcinosis. Mutations within this gene may underlie other forms of genetic epilepsy and febrile seizures.
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PMID:Autosomal dominant early childhood seizures associated with chondrocalcinosis and a mutation in the ANKH Gene. 1546 80

Abnormally synchronized synaptic transmission in the brain causes epilepsy. Most inherited forms of epilepsy result from mutations in ion channels. However, one form of epilepsy, autosomal dominant partial epilepsy with auditory features (ADPEAF), is characterized by mutations in a secreted neuronal protein, LGI1. We show that ADAM22, a transmembrane protein that when mutated itself causes seizure, serves as a receptor for LGI1. LGI1 enhances AMPA receptor-mediated synaptic transmission in hippocampal slices. The mutated form of LGI1 fails to bind to ADAM22. ADAM22 is anchored to the postsynaptic density by cytoskeletal scaffolds containing stargazin. These studies in rat brain indicate possible avenues for understanding human epilepsy.
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PMID:Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. 1769 71

CD45, also called leucocyte common antigen is a transmembrane protein tyrosine phosphatase on the surface of nearly all white blood cells and has a functional role in signal transduction. In the brain, the expression of CD45 can be used to distinguish microglial cells with a characteristic phenotype of CD11b/c+ and CD45(low) from other central nervous system (CNS) macrophages which show an expression of CD11b/c+ and CD45(high). In the course of pathological changes in the CNS, microglia in rodents is known to readily upregulate expression of various surface molecules, such as CD45. Understanding the mechanisms that regulate expression of surface molecules is essential to study the pathogenesis of CNS diseases. In the present study, the expression of CD45 on microglia of 42 dogs was examined ex vivo by means of flow cytometry. The dogs were classified in two groups according to the histopathological diagnosis in the CNS. All dogs without changes in the CNS (group I; n = 22) only showed low percentages of CD45+ microglial cells. In group II consisting of 20 dogs with different intracranial diseases varying results were obtained. Thirteen dogs showed a low percentage of CD45+ microglial cells whereas seven dogs exhibited high percentages of microglial cells expressing CD45. Evaluation of expression intensity in these seven dogs revealed two subpopulations of CD45+ microglial cells: a large subpopulation with CD45(low) and a small subpopulation with CD45(high). The expression intensity of CD45(high) was comparable with that of canine monocytes. It was attempted to correlate these findings to age of the animals, underlying disease, duration of clinical signs, medical treatment, occurrence of seizure activity and the expression of other surface molecules. It appeared that dogs with high percentages of CD45+ suffered from long-lasting CNS disease with seizures. In future studies, the reason and consequences for upregulated CD45 in long-lasting CNS diseases has to be further evaluated.
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PMID:Differential expression of CD45 on canine microglial cells. 1765 Jan 52

Juvenile neuronal ceroid-lipofuscinosis (JNCL, Batten disease, Spielmeyer-Vogt-Sjogren disease, CLN3) is the most common inherited, autosomal recessive, neurodegenerative disorder in man. Like the other neuronal ceroid-lipofuscinoses, it is characterized by progressive loss of vision, seizures, and loss of cognitive and motor functions, leading to premature demise. JNCL is caused by mutations of CLN3, a gene that encodes a hydrophobic transmembrane protein, which localizes to membrane lipid rafts in lysosomes, endosomes, synaptosomes, and cell membrane. While the primary function of the CLN3 protein (CLN3P) may be debated, its absence affects numerous cellular functions including pH regulation, arginine transport, membrane trafficking, and apoptosis. We have recently suggested that the unifying primary function of CLN3P may be in a novel palmitoyl-protein Delta-9 desaturase (PPD) activity that in our opinion could explain all of the various functional abnormalities seen in the JNCL cells. Another group of researchers has recently shown a correlation between the CLN3P expression and the synthesis of bis(monoacylglycerol)phosphate (BMP) and suggested that CLN3P may play a role in the biosynthesis of BMP. In this review, following an introduction to the neuronal ceroid-lipofuscinoses, we provide a brief overview and an update of the most recent research in JNCL, specifically that related to the function of CLN3P.
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PMID:Juvenile neuronal ceroid-lipofuscinosis (Batten disease): a brief review and update. 1789 96

Recessive inheritance of mutations in ceroid neuronal lipofuscinosis type 3 (CLN3) results in juvenile neuronal ceroid lipofuscinosis (JNCL), a childhood neurodegenerative disease with symptoms including loss of vision, seizures, and motor and mental decline. CLN3p is a transmembrane protein with undefined function. Using a Cln3 reporter mouse harboring a nuclear-localized bacterial beta-galactosidase (beta-Gal) gene driven by the native Cln3 promoter, we detected beta-Gal most prominently in epithelial cells of skin, colon, lung, and kidney. In the kidney, beta-Gal-positive nuclei were predominant in medullary collecting duct principal cells, with increased expression along the medullary osmotic gradient. Quantification of Cln3 transcript levels from kidneys of wild-type (Cln3(+/+)) mice corroborated this expression gradient. Reporter mouse-derived renal epithelial cultures demonstrated a tonicity-dependent increase in beta-Gal expression. RT-quantitative PCR determination of Cln3 transcript levels further supported osmoregulation at the Cln3 locus. In vivo, osmoresponsiveness of Cln3 was demonstrated by reduction of medullary Cln3 transcript abundance after furosemide administration. Primary cultures of epithelial cells of the inner medulla from Cln3(lacZ/lacZ) (CLN3p-null) mice showed no defect in osmolyte accumulation or taurine flux, arguing against a requirement for CLN3p in osmolyte import or synthesis. CLN3p-deficient mice with free access to water showed a mild urine-concentrating defect but, upon water deprivation, were able to concentrate their urine normally. Unexpectedly, we found that CLN3p-deficient mice were hyperkalemic and had a low fractional excretion of K(+). Together, these findings suggest an osmoregulated role for CLN3p in renal control of water and K(+) balance.
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PMID:Osmoregulation of ceroid neuronal lipofuscinosis type 3 in the renal medulla. 2021 47

The seizure-related gene 6 (Sez-6) encodes a transmembrane protein that is expressed in neuronal cells. A Sez-6-deficient mouse exhibits impaired spatial memory, motor deficits, and decreased anxiety levels. To understand the function of Sez-6 during the postnatal development of the forebrain, the spatiotemporal pattern of distribution of the Sez-6 protein was immunohistochemically analyzed using a new anti-Sez-6 antibody. Western blot analysis confirmed the specificity of this new antibody, and showed that the content of the Sez-6 protein in the cerebral cortex was highest during the neonatal period and decreased gradually thereafter. Immunohistochemical analysis revealed that Sez-6 immunoreactivity (IR) was detected in various brain regions, such as the hippocampus, cerebral cortex, piriform cortex, striatum, lateral amygdala, and olfactory tubercle. The expression patterns of Sez-6 in these brain regions was divided into three groups: i) in the cerebral cortex, hippocampus, and lateral amygdala, moderate-to-strong Sez-6 IR was detected in the first postnatal week and decreased gradually thereafter; ii) Sez-6 IR was not observed during the neonatal period in the striatum and the intensity of the signal increased gradually toward adulthood; and iii) strong Sez-6 IR was observed in the olfactory tubercle, regardless of the developmental stage. Furthermore, Sez-6 IR was detected in dendrites of hippocampal and cortical pyramidal neurons neonatally, whereas it localized around the soma after postnatal day 10. These spatiotemporal alterations of the regional and intracellular distribution of the Sez-6 protein suggest multiple functions for this protein during the postnatal development of the forebrain.
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PMID:The distribution of the seizure-related gene 6 (Sez-6) protein during postnatal development of the mouse forebrain suggests multiple functions for this protein: an analysis using a new antibody. 2133 15

Loss-of-function mutations in CLN3 are responsible for juvenile-onset neuronal ceroid lipofuscinosis (JNCL), or Batten disease, which is an incurable lysosomal disease that manifests with vision loss, followed by seizures and progressive neurodegeneration, robbing children of motor skills, speech and cognition, and eventually leading to death in the second or third decade of life. Emerging clinical evidence points to JNCL pathology outside of the CNS, including the cardiovascular system. The CLN3 gene encodes an unusual transmembrane protein, CLN3 or battenin, whose elusive function has been the subject of intense study for more than 10 years. Owing to the detailed characterization of a large number of disease models, our knowledge of CLN3 protein function is finally coming into focus. This review will describe the most current understanding of CLN3 structure, function and dysfunction in JNCL.
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PMID:The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking. 2254 70


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