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[PMID]:29348429
[Au] Autor:Goto-Ito S; Yamagata A; Sato Y; Uemura T; Shiroshima T; Maeda A; Imai A; Mori H; Yoshida T; Fukai S
[Ad] Endereço:Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, 113-0032, Japan.
[Ti] Título:Structural basis of trans-synaptic interactions between PTPδ and SALMs for inducing synapse formation.
[So] Source:Nat Commun;9(1):269, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Synapse formation is triggered by trans-synaptic interactions of cell adhesion molecules, termed synaptic organizers. Three members of type-II receptor protein tyrosine phosphatases (classified as type-IIa RPTPs; PTPδ, PTPσ and LAR) are known as presynaptic organizers. Synaptic adhesion-like molecules (SALMs) have recently emerged as a family of postsynaptic organizers. Although all five SALM isoforms can bind to the type-IIa RPTPs, only SALM3 and SALM5 reportedly have synaptogenic activities depending on their binding. Here, we report the crystal structures of apo-SALM5, and PTPδ-SALM2 and PTPδ-SALM5 complexes. The leucine-rich repeat (LRR) domains of SALMs interact with the second immunoglobulin-like (Ig) domain of PTPδ, whereas the Ig domains of SALMs interact with both the second and third Ig domains of PTPδ. Unexpectedly, the structures exhibit the LRR-mediated 2:2 complex. Our synaptogenic co-culture assay using site-directed SALM5 mutants demonstrates that presynaptic differentiation induced by PTPδ-SALM5 requires the dimeric property of SALM5.
[Mh] Termos MeSH primário: Moléculas de Adesão Celular Neuronais/química
Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/química
Sinapses/metabolismo
Transmissão Sináptica
[Mh] Termos MeSH secundário: Animais
Moléculas de Adesão Celular Neuronais/genética
Moléculas de Adesão Celular Neuronais/metabolismo
Cristalografia por Raios X
Células HEK293
Seres Humanos
Modelos Moleculares
Mutação
Ligação Proteica
Domínios Proteicos
Isoformas de Proteínas/química
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Multimerização Proteica
Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética
Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Adhesion Molecules, Neuronal); 0 (Protein Isoforms); 0 (SALM5 protein, human); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02417-z


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[PMID]:29348579
[Au] Autor:Lin Z; Liu J; Ding H; Xu F; Liu H
[Ad] Endereço:State Key Laboratory of Natural and Biomimetic Drugs & Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
[Ti] Título:Structural basis of SALM5-induced PTPδ dimerization for synaptic differentiation.
[So] Source:Nat Commun;9(1):268, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:SALM5, a synaptic adhesion molecule implicated in autism, induces presynaptic differentiation through binding to the LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that have been highlighted as presynaptic hubs for synapse formation. The mechanisms underlying SALM5/LAR-RPTP interaction remain unsolved. Here we report crystal structures of human SALM5 LRR-Ig alone and in complex with human PTPδ Ig1-3 (MeA ). Distinct from other LAR-RPTP ligands, SALM5 mainly exists as a dimer with LRR domains from two protomers packed in an antiparallel fashion. In the 2:2 heterotetrameric SALM5/PTPδ complex, a SALM5 dimer bridges two separate PTPδ molecules. Structure-guided mutations and heterologous synapse formation assays demonstrate that dimerization of SALM5 is prerequisite for its functionality in inducing synaptic differentiation. This study presents a structural template for the SALM family and reveals a mechanism for how a synaptic adhesion molecule directly induces cis-dimerization of LAR-RPTPs into higher-order signaling assembly.
[Mh] Termos MeSH primário: Moléculas de Adesão Celular Neuronais/metabolismo
Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo
[Mh] Termos MeSH secundário: Baculoviridae
Dimerização
Células HEK293
Seres Humanos
Domínios de Imunoglobulina
Estrutura Quaternária de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Adhesion Molecules, Neuronal); 0 (SALM5 protein, human); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 2)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02414-2


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[PMID]:29244827
[Au] Autor:Henderson HJ; Karanam B; Samant R; Vig K; Singh SR; Yates C; Bedi D
[Ad] Endereço:Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL, United States of America.
[Ti] Título:Neuroligin 4X overexpression in human breast cancer is associated with poor relapse-free survival.
[So] Source:PLoS One;12(12):e0189662, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The molecular mechanisms involved in breast cancer progression and metastasis still remain unclear to date. It is a heterogeneous disease featuring several different phenotypes with consistently different biological characteristics. Neuroligins are neural cell adhesion molecules that have been implicated in heterotopic cell adhesion. In humans, alterations in neuroligin genes are implicated in autism and other cognitive diseases. Until recently, neuroligins have been shown to be abundantly expressed in blood vessels and also play a role implicated in the growth of glioma cells. Here we report increased expression of neuroligin 4X (NLGN4X) in breast cancer. We found NLGN4X was abundantly expressed in breast cancer tissues. NLGN4X expression data for all breast cancer cell lines in the Cancer Cell Line Encyclopedia (CCLE) was analyzed. Correlation between NLGN4X levels and clinicopathologic parameters were analyzed within Oncomine datasets. Evaluation of these bioinfomatic datasets results revealed that NLGN4X expression was higher in triple negative breast cancer cells, particularly the basal subtype and tissues versus non-triple-negative sets. Its level was also observed to be higher in metastatic tissues. RT-PCR, flow cytometry and immunofluorescence study of MDA-MB-231 and MCF-7 breast cancer cells validated that NLGN4X was increased in MDA-MB-231. Knockdown of NLGN4X expression by siRNA decreased cell proliferation and migration significantly in MDA-MB-231 breast cancer cells. NLGN4X knockdown in MDA-MB-231 cells resulted in induction of apoptosis as determined by annexin staining, elevated caspase 3/7 and cleaved PARP by flow cytometry. High NLGN4X expression highly correlated with decrease in relapse free-survival in TNBC. NLGN4X might represent novel biomarkers and therapeutic targets for breast cancer. Inhibition of NLGN4X may be a new target for the prevention and treatment of breast cancer.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Moléculas de Adesão Celular Neuronais/genética
Recidiva Local de Neoplasia/genética
Neoplasias de Mama Triplo Negativas/genética
[Mh] Termos MeSH secundário: Apoptose/genética
Proliferação Celular/genética
Intervalo Livre de Doença
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Células MCF-7
Metástase Neoplásica
Recidiva Local de Neoplasia/patologia
Neoplasias de Mama Triplo Negativas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Cell Adhesion Molecules, Neuronal); 0 (NLGN4X protein, human)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189662


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[PMID]:28953682
[Au] Autor:Han L; Jia Z; Cao C; Liu Z; Liu F; Wang L; Ren W; Sun M; Wang B; Li C; Chen L
[Ad] Endereço:aDepartment of Endocrinology Qilu Hospital of Shandong University, Jinan bGout Laboratory, The Affiliated Hospital of Qingdao University, Qingdao cState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
[Ti] Título:Potential contribution of the neurodegenerative disorders risk loci to cognitive performance in an elderly male gout population.
[So] Source:Medicine (Baltimore);96(39):e8195, 2017 Sep.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cognitive impairment has been described in elderly subjects with high normal concentrations of serum uric acid. However, it remains unclear if gout confers an increased poorer cognition than those in individuals with asymptomatic hyperuricemia. The present study aimed at evaluating cognitive function in patients suffering from gout in an elderly male population, and further investigating the genetic contributions to the risk of cognitive function.This study examined the cognitive function as assessed by Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in 205 male gout patients and 204 controls. The genetic basis of these cognitive measures was evaluated by genome-wide association study (GWAS) data in 102 male gout patients. Furthermore, 7 loci associated with cognition in GWAS were studied for correlation with gout in 1179 male gout patients and 1848 healthy male controls.Compared with controls, gout patients had significantly lower MoCA scores [22.78 ±â€Š3.01 vs 23.42 ±â€Š2.95, P = .023, adjusted by age, body mass index (BMI), education, and emotional disorder]. GWAS revealed 7 single-nucleotide polymorphisms (SNPs) associations with MoCA test at a level of conventional genome-wide significance (P < 9.6 × 10). The most significant association was observed between rs12895072 and rs12434554 within the KTN1 gene (Padjusted = 4.2 × 10, Padjusted = 4.7 × 10) at 14q22. The next best signal was in RELN gene (rs155333, Padjusted = 1.3 × 10) at 7q22, while the other variants at rs17458357 (Padjusted = 3.98 × 10), rs2572683 (Padjusted = 8.9 × 10), rs12555895 (Padjusted = 2.6 × 10), and rs3764030 (Padjusted = 9.4 × 10) were also statistically significant. The 7 SNPs were not associated with gout in further analysis (all P > .05).Elderly male subjects with gout exhibit accelerated decline in cognition performance. Several neurodegenerative disorders risk loci were identified for genetic contributors to cognitive performance in our Chinese elderly male gout population. Larger prospective studies of the cognitive performance and genetic analysis in gout subjects are recommended.
[Mh] Termos MeSH primário: Moléculas de Adesão Celular Neuronais/genética
Cognição/fisiologia
Proteínas da Matriz Extracelular/genética
Gota
Proteínas de Membrana/genética
Proteínas do Tecido Nervoso/genética
Transtornos Neurocognitivos
Serina Endopeptidases/genética
[Mh] Termos MeSH secundário: Idoso
China/epidemiologia
Testes Genéticos
Estudo de Associação Genômica Ampla
Gota/sangue
Gota/complicações
Gota/epidemiologia
Gota/psicologia
Seres Humanos
Testes de Inteligência
Masculino
Meia-Idade
Transtornos Neurocognitivos/diagnóstico
Transtornos Neurocognitivos/epidemiologia
Transtornos Neurocognitivos/genética
Transtornos Neurocognitivos/fisiopatologia
Polimorfismo de Nucleotídeo Único
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Adhesion Molecules, Neuronal); 0 (Extracellular Matrix Proteins); 0 (KTN1 protein, human); 0 (Membrane Proteins); 0 (Nerve Tissue Proteins); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.- (reelin protein)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008195


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[PMID]:28942923
[Au] Autor:Paul A; Crow M; Raudales R; He M; Gillis J; Huang ZJ
[Ad] Endereço:Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
[Ti] Título:Transcriptional Architecture of Synaptic Communication Delineates GABAergic Neuron Identity.
[So] Source:Cell;171(3):522-539.e20, 2017 Oct 19.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Understanding the organizational logic of neural circuits requires deciphering the biological basis of neuronal diversity and identity, but there is no consensus on how neuron types should be defined. We analyzed single-cell transcriptomes of a set of anatomically and physiologically characterized cortical GABAergic neurons and conducted a computational genomic screen for transcriptional profiles that distinguish them from one another. We discovered that cardinal GABAergic neuron types are delineated by a transcriptional architecture that encodes their synaptic communication patterns. This architecture comprises 6 categories of ∼40 gene families, including cell-adhesion molecules, transmitter-modulator receptors, ion channels, signaling proteins, neuropeptides and vesicular release components, and transcription factors. Combinatorial expression of select members across families shapes a multi-layered molecular scaffold along the cell membrane that may customize synaptic connectivity patterns and input-output signaling properties. This molecular genetic framework of neuronal identity integrates cell phenotypes along multiple axes and provides a foundation for discovering and classifying neuron types.
[Mh] Termos MeSH primário: Neurônios GABAérgicos/citologia
Perfilação da Expressão Gênica
Análise de Célula Única
[Mh] Termos MeSH secundário: Animais
Moléculas de Adesão Celular Neuronais/metabolismo
Matriz Extracelular/metabolismo
Neurônios GABAérgicos/metabolismo
Camundongos
Receptores de GABA/metabolismo
Receptores Ionotrópicos de Glutamato/metabolismo
Transdução de Sinais
Sinapses
Transcrição Genética
Zinco/metabolismo
Ácido gama-Aminobutírico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Adhesion Molecules, Neuronal); 0 (Receptors, GABA); 0 (Receptors, Ionotropic Glutamate); 56-12-2 (gamma-Aminobutyric Acid); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171104
[Lr] Data última revisão:
171104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE


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[PMID]:28939043
[Au] Autor:Sato Y; Suzuki S; Iijima Y; Iijima T
[Ad] Endereço:Institute of Innovative Science and Technology, Medical Division, Tokai University, Isehara City, Kanagawa, Japan; Department of Chemistry and Bioresource, Faculty of Engineering, Tokai University, Hiratsuka City, Kanagawa, Japan.
[Ti] Título:Neuroligin-induced presynaptic differentiation through SLM2-mediated splicing modifications of neurexin in cerebellar cultures.
[So] Source:Biochem Biophys Res Commun;493(2):1030-1036, 2017 Nov 18.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neurexins (NRXs) and neuroligins (NLs) play important roles in synapse specification. The alternatively spliced segment 4 (AS4) of NRX genes (Nrxn) is a critical element in selective trans-synaptic interactions. However, the role of splicing of NRXs and NLs in synapse specification is not fully understood. To investigate the exact role of splice-dependent NRX-NL interaction in the specification of glutamatergic and gamma-aminobutyric acid (GABA)-ergic synapses in the cerebellum, we evaluated the synaptogenic receptor activity of NL1/2/3 isoforms in a neuron-fibroblast co-culture system, in which the Nrxn AS4 segments are manipulated using SLM2, a selective and dominant regulator of AS4 splicing. We show that ectopic SLM2 expression (SLM2 E/E) causes marked skipping of exon 20 of AS4 in cerebellar neuron culture. Whereas NLs can induce VAMP2 presynaptic contacts from mainly glutamatergic neurons in both uninfected (control) and SLM2 E/E co-cultures, they induce VGAT GABAergic contacts in the control culture, but not properly in the SLM2 E/E culture. Furthermore, Nrxn3 is responsible for the NL-induced assembly of GABAergic synapses in co-culture. Importantly, lentivirus-based expression of Nrxn3 containing exon 20 restores the reduced NL-induced GABAergic contacts in the SLM2 E/E co-culture. Therefore, our findings may provide further insights into NRX-NL mediated synapse specification.
[Mh] Termos MeSH primário: Processamento Alternativo
Moléculas de Adesão Celular Neuronais/metabolismo
Cerebelo/citologia
Proteínas de Membrana/metabolismo
Proteínas do Tecido Nervoso/genética
Proteínas do Tecido Nervoso/metabolismo
Proteínas de Ligação a RNA/metabolismo
[Mh] Termos MeSH secundário: Animais
Moléculas de Adesão Celular Neuronais/genética
Células Cultivadas
Cerebelo/metabolismo
Técnicas de Cocultura
Células HEK293
Seres Humanos
Camundongos Endogâmicos ICR
Moléculas de Adesão de Célula Nervosa/genética
Moléculas de Adesão de Célula Nervosa/metabolismo
Neurônios/citologia
Neurônios/metabolismo
Proteínas de Ligação a RNA/genética
Sinapses/metabolismo
Ácido gama-Aminobutírico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Adhesion Molecules, Neuronal); 0 (Cntnap1 protein, mouse); 0 (Khdrbs3 protein, mouse); 0 (Membrane Proteins); 0 (Nerve Tissue Proteins); 0 (Neural Cell Adhesion Molecules); 0 (Nrxn1 protein, mouse); 0 (RNA-Binding Proteins); 0 (neurexin 3, mouse); 0 (neurexin II); 0 (neuroligin 1); 0 (neuroligin 2); 0 (neuroligin 3); 56-12-2 (gamma-Aminobutyric Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170924
[St] Status:MEDLINE


  7 / 4739 MEDLINE  
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[PMID]:28887403
[Au] Autor:Santana J; Marzolo MP
[Ad] Endereço:Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
[Ti] Título:The functions of Reelin in membrane trafficking and cytoskeletal dynamics: implications for neuronal migration, polarization and differentiation.
[So] Source:Biochem J;474(18):3137-3165, 2017 Sep 07.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Reelin is a large extracellular matrix protein with relevant roles in mammalian central nervous system including neurogenesis, neuronal polarization and migration during development; and synaptic plasticity with its implications in learning and memory, in the adult. Dysfunctions in reelin signaling are associated with brain lamination defects such as lissencephaly, but also with neuropsychiatric diseases like autism, schizophrenia and depression as well with neurodegeneration. Reelin signaling involves a core pathway that activates upon reelin binding to its receptors, particularly ApoER2 (apolipoprotein E receptor 2)/LRP8 (low-density lipoprotein receptor-related protein 8) and very low-density lipoprotein receptor, followed by Src/Fyn-mediated phosphorylation of the adaptor protein Dab1 (Disabled-1). Phosphorylated Dab1 (pDab1) is a hub in the signaling cascade, from which several other downstream pathways diverge reflecting the different roles of reelin. Many of these pathways affect the dynamics of the actin and microtubular cytoskeleton, as well as membrane trafficking through the regulation of the activity of small GTPases, including the Rho and Rap families and molecules involved in cell polarity. The complexity of reelin functions is reflected by the fact that, even now, the precise mode of action of this signaling cascade at the cellular and molecular levels remains unclear. This review addresses and discusses in detail the participation of reelin in the processes underlying neurogenesis, neuronal migration in the cerebral cortex and the hippocampus; and the polarization, differentiation and maturation processes that neurons experiment in order to be functional in the adult brain. and evidence is presented in order to facilitate a better understanding of this fascinating system.
[Mh] Termos MeSH primário: Moléculas de Adesão Celular Neuronais/metabolismo
Diferenciação Celular
Membrana Celular/metabolismo
Movimento Celular
Citoesqueleto/metabolismo
Proteínas da Matriz Extracelular/metabolismo
Proteínas do Tecido Nervoso/metabolismo
Neurônios/citologia
Neurônios/fisiologia
Serina Endopeptidases/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cell Adhesion Molecules, Neuronal); 0 (Extracellular Matrix Proteins); 0 (Nerve Tissue Proteins); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.- (reelin protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170910
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20160628


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[PMID]:28878050
[Au] Autor:Escudero D; Guasp M; Ariño H; Gaig C; Martínez-Hernández E; Dalmau J; Graus F
[Ad] Endereço:From the Service of Neurology (D.E., M.G., C.G., J.D., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., C.G., E.M.-H., J.D., F.G.), Institut d'Investigació Biomèdica August Pi i Sunyer; Institució Catalana de Recerca i Estudis Avançats (J.D.), Barcelona, Spain; and Dep
[Ti] Título:Antibody-associated CNS syndromes without signs of inflammation in the elderly.
[So] Source:Neurology;89(14):1471-1475, 2017 Oct 03.
[Is] ISSN:1526-632X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To report the CNS syndromes of patients ≥60 years of age with antibodies against neuronal surface antigens but no evidence of brain MRI and CSF inflammatory changes. METHODS: This was a retrospective clinical analysis of patients with antibodies against neuronal surface antigens who fulfilled 3 criteria: age ≥60 years, no inflammatory abnormalities in brain MRI, and no CSF pleocytosis. Antibodies were determined with reported techniques. RESULTS: Among 155 patients ≥60 years of age with neurologic syndromes related to antibodies against neuronal surface antigens, 35 (22.6%) fulfilled the indicated criteria. The median age of these 35 patients was 68 years (range 60-88 years). Clinical manifestations included faciobrachial dystonic seizures (FBDS) in 11 of 35 (31.4%) patients, all with LGI1 antibodies; a combination of gait instability, brainstem dysfunction, and sleep disorder associated with IgLON5 antibodies in 10 (28.6%); acute confusion, memory loss, and behavioral changes suggesting autoimmune encephalitis (AE) in 9 (25.7%; 2 patients with AMPAR, 2 with NMDAR, 2 with GABAbR, 2 with LGI1, and 1 with CASPR2 antibodies); and rapidly progressive cognitive deterioration in 5 (14.3%; 3 patients with IgLON5 antibodies, 1 with chorea; 1 with DPPX antibody-associated cerebellar ataxia and arm rigidity; and 1 with CASPR2 antibodies). CONCLUSIONS: In patients ≥60 years of age, the correct identification of characteristic CNS syndromes (FBDS, anti-IgLON5 syndrome, AE) should prompt antibody testing even without evidence of inflammation in MRI and CSF studies. Up to 15% of the patients developed rapidly progressive cognitive deterioration, which further complicated the differential diagnosis with a neurodegenerative disorder.
[Mh] Termos MeSH primário: Anticorpos/metabolismo
Sistema Nervoso Central/imunologia
Sistema Nervoso Central/metabolismo
Doenças do Sistema Nervoso/imunologia
Doenças do Sistema Nervoso/patologia
[Mh] Termos MeSH secundário: Fatores Etários
Idoso
Idoso de 80 Anos ou mais
Envelhecimento
Moléculas de Adesão Celular Neuronais/imunologia
Feminino
Células HEK293
Seres Humanos
Inflamação
Masculino
Meia-Idade
Proteínas/imunologia
Receptores de GABA-B/imunologia
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (Cell Adhesion Molecules, Neuronal); 0 (IgLON5 protein, human); 0 (LGI1 protein, human); 0 (Proteins); 0 (Receptors, GABA-B)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE
[do] DOI:10.1212/WNL.0000000000004541


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[PMID]:28841651
[Au] Autor:Nakanishi M; Nomura J; Ji X; Tamada K; Arai T; Takahashi E; Bucan M; Takumi T
[Ad] Endereço:RIKEN Brain Science Institute, Wako, Saitama, Japan.
[Ti] Título:Functional significance of rare neuroligin 1 variants found in autism.
[So] Source:PLoS Genet;13(8):e1006940, 2017 Aug.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Genetic mutations contribute to the etiology of autism spectrum disorder (ASD), a common, heterogeneous neurodevelopmental disorder characterized by impairments in social interaction, communication, and repetitive and restricted patterns of behavior. Since neuroligin3 (NLGN3), a cell adhesion molecule at the neuronal synapse, was first identified as a risk gene for ASD, several additional variants in NLGN3 and NLGN4 were found in ASD patients. Moreover, synaptopathies are now known to cause several neuropsychiatric disorders including ASD. In humans, NLGNs consist of five family members, and neuroligin1 (NLGN1) is a major component forming a complex on excitatory glutamatergic synapses. However, the significance of NLGN1 in neuropsychiatric disorders remains unknown. Here, we systematically examine five missense variants of NLGN1 that were detected in ASD patients, and show molecular and cellular alterations caused by these variants. We show that a novel NLGN1 Pro89Leu (P89L) missense variant found in two ASD siblings leads to changes in cellular localization, protein degradation, and to the impairment of spine formation. Furthermore, we generated the knock-in P89L mice, and we show that the P89L heterozygote mice display abnormal social behavior, a core feature of ASD. These results, for the first time, implicate rare variants in NLGN1 as functionally significant and support that the NLGN synaptic pathway is of importance in the etiology of neuropsychiatric disorders.
[Mh] Termos MeSH primário: Transtorno do Espectro Autista/genética
Moléculas de Adesão Celular Neuronais/genética
Predisposição Genética para Doença
Comportamento Social
Coluna Vertebral/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Animais
Transtorno do Espectro Autista/fisiopatologia
Comportamento Animal/fisiologia
Modelos Animais de Doenças
Feminino
Seres Humanos
Masculino
Camundongos
Camundongos Transgênicos
Mutação de Sentido Incorreto/genética
Neurônios/patologia
Linhagem
Proteólise
Coluna Vertebral/fisiopatologia
Sinapses/genética
Sinapses/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Adhesion Molecules, Neuronal); 0 (neuroligin 1)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006940


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[PMID]:28837701
[Au] Autor:Kudumala SR; Penserga T; Börner J; Slipchuk O; Kakad P; Lee LH; Qureshi A; Pielage J; Godenschwege TA
[Ad] Endereço:Department of Biological Sciences, Florida Atlantic University, Jupiter, Florida, United States of America.
[Ti] Título:Lissencephaly-1 dependent axonal retrograde transport of L1-type CAM Neuroglian in the adult drosophila central nervous system.
[So] Source:PLoS One;12(8):e0183605, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Here, we established the Drosophila Giant Fiber neurons (GF) as a novel model to study axonal trafficking of L1-type Cell Adhesion Molecules (CAM) Neuroglian (Nrg) in the adult CNS using live imaging. L1-type CAMs are well known for their importance in nervous system development and we previously demonstrated a role for Nrg in GF synapse formation. However, in the adult they have also been implicated in synaptic plasticity and regeneration. In addition, to its canonical role in organizing cytoskeletal elements at the plasma membrane, vertebrate L1CAM has also been shown to regulate transcription indirectly as well as directly via its import to the nucleus. Here, we intend to determine if the sole L1CAM homolog Nrg is retrogradley transported and thus has the potential to relay signals from the synapse to the soma. Live imaging of c-terminally tagged Nrg in the GF revealed that there are at least two populations of retrograde vesicles that differ in speed, and either move with consistent or varying velocity. To determine if endogenous Nrg is retrogradely transported, we inhibited two key regulators, Lissencephaly-1 (Lis1) and Dynactin, of the retrograde motor protein Dynein. Similar to previously described phenotypes for expression of poisonous subunits of Dynactin, we found that developmental knock down of Lis1 disrupted GF synaptic terminal growth and that Nrg vesicles accumulated inside the stunted terminals in both mutant backgrounds. Moreover, post mitotic Lis1 knock down in mature GFs by either RNAi or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) induced mutations, resulted in normal length terminals with fully functional GF synapses which also exhibited severe accumulation of endogenous Nrg vesicles. Thus, our data suggests that accumulation of Nrg vesicles is due to failure of retrograde transport rather than a failure of terminal development. Together with the finding that post mitotic knock down of Lis1 also disrupted retrograde transport of tagged Nrg vesicles in GF axons, it demonstrates that endogenous Nrg protein is transported from the synapse to the soma in the adult central nervous system in a Lis1-dependent manner.
[Mh] Termos MeSH primário: Moléculas de Adesão Celular Neuronais/metabolismo
Sistema Nervoso Central/metabolismo
Proteínas de Drosophila/metabolismo
Drosophila/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
Moléculas de Adesão Celular Neuronais/genética
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
Proteínas de Drosophila/genética
Técnicas de Silenciamento de Genes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Adhesion Molecules, Neuronal); 0 (Drosophila Proteins); 127496-12-2 (Nrg protein, Drosophila)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183605



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