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https://www.readbyqxmd.com/read/28433501/disrupted-in-schizophrenia-1-regulates-the-processing-of-reelin-in-the-perinatal-cortex
#1
Nicholas J Bradshaw, Svenja V Trossbach, Sabrina Köber, Susanne Walter, Ingrid Prikulis, Sascha Weggen, Carsten Korth
Disrupted in Schizophrenia 1 (DISC1) is a prominent gene in mental illness research, encoding a scaffold protein known to be of importance in the developing cerebral cortex. Reelin is a critical extracellular protein for development and lamination of the prenatal cortex and which has also been independently implicated in mental illness. Regulation of reelin activity occurs through processing by the metalloproteinases ADAMTS-4 and ADAMTS-5. Through cross-breeding of heterozygous transgenic DISC1 mice with heterozygous reeler mice, which have reduced reelin, pups heterozygous for both phenotypes were generated...
April 19, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28419454/the-de-novo-autism-spectrum-disorder-reln-r2290c-mutation-reduces-reelin-secretion-and-increases-protein-disulfide-isomerase-expression
#2
Dawn B Lammert, Frank A Middleton, Jen Pan, Eric C Olson, Brian W Howell
Despite the recent identification of over 40 missense heterozygous RELN mutations in ASD, none of these has been functionally characterized. Reelin is an integral signaling ligand for proper brain development and postnatal synapse function - properties likely disrupted in ASD patients. We find that the R2290C mutation, which arose de novo in an affected ASD proband, and other analogous mutations in RXR domains reduce protein secretion. Closer analysis of RELN R2290C heterozygous neurospheres reveals upregulation of Protein Disulfide Isomerase A1, best known as an ER-chaperone protein, which has been linked to neuronal pathology...
April 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28418356/-pathomorphology-of-the-ventricular-germinal-zone-and-neocortex-in-newborn-infants-with-posthemorrhagic-hydrocephalus
#3
E V Protsenko, L P Peretyatko, O P Saryeva
AIM: Тo study the morphological features of the ventricular germinal zone and neocortex in newborns at 22-40 weeks' gestation with posthemorrhagic hydrocephalus. MATERIAL AND METHODS: The brains of fetuses and newborns at 22-40 weeks' gestation with posthemorrhagic hydrocephalus (n=12) were examined; a control group included the brains with a lateral ventricle lumen width of not more than 0.5 cm (n=30). The investigators conducted a comprehensive pathomorphological study of the ventricular germinal zone and neocortex in the projection field No...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28385118/neuroprotective-effect-of-melatonin-on-soluble-a%C3%AE-1-42-induced-cortical-neurodegeneration-via-reelin-dab1-signaling-pathway
#4
Chunli Hu, Pan Wang, Shuman Zhang, Lili Ren, Yiheng Lv, Rui Yin, Jing Bi
OBJECTIVE: Soluble Aβ1-42 oligomers play a vital role in the development and pathogenesis of Alzheimer's disease (AD). Melatonin could delay the progress of AD through multiple mechanisms. Reelin-Dab1 signaling plays an important role in AD, including neuronal function and synaptic plasticity. However, whether melatonin could exert its neuroprotective function against soluble Aβ1-42-induced neurotoxicity during AD development through regulating Reelin-Dab1 signaling remains poorly understood...
April 7, 2017: Neurological Research
https://www.readbyqxmd.com/read/28348420/reelin-expression-in-human-liver-of-patients-with-chronic-hepatitis-c-infection
#5
Simone Carotti, Giuseppe Perrone, Michelina Amato, Umberto Vespasiani Gentilucci, Daniela Righi, Maria Francesconi, Claudio Pellegrini, Francesca Zalfa, Maria Zingariello, Antonio Picardi, Andrea Onetti Muda, Sergio Morini
Reelin is a secreted extracellular glycoprotein that plays a critical role during brain development. Several studies have described Reelin expression in hepatic stellate cells of the human liver. In order to investigate the possible role of Reelin in the process of hepatic fibrogenesis, in this study we investigated Reelin expression in the liver tissue of patients infected with the Hepatitis C Virus (HCV). On this basis, Reelin expression was analysed by immunohistochemistry during liver biopsies of 81 patients with HCV-related chronic hepatitis...
March 17, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28345605/extracellular-matrix-protein-reelin-promotes-myeloma-progression-by-facilitating-tumor-cell-proliferation-and-glycolysis
#6
Xiaodan Qin, Liang Lin, Li Cao, Xinwei Zhang, Xiao Song, Jie Hao, Yan Zhang, Risheng Wei, Xiaojun Huang, Jin Lu, Qing Ge
Reelin is an extracellular matrix protein that is crucial for neuron migration, adhesion, and positioning. We examined the expression of Reelin in a large cohort of multiple myeloma patients recorded in Gene Expression Omnibus (GEO) database and used over-expression and siRNA knockdown of Reelin to investigate the role of Reelin in myeloma cell growth. We find that Reelin expression is negatively associated with myeloma prognosis. Reelin promotes myeloma cell proliferation in vitro as well as in vivo. The Warburg effect, evidenced by increased glucose uptake and lactate production, is also enhanced in Reelin-expressing cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298885/functional-roles-of-the-interaction-of-app-and-lipoprotein-receptors
#7
REVIEW
Theresa Pohlkamp, Catherine R Wasser, Joachim Herz
The biological fates of the key initiator of Alzheimer's disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28292942/the-apoe-receptors-vldlr-and-apoer2-in-central-nervous-system-function-and-disease
#8
Courtney Lane-Donovan, Joachim Herz
The low-density lipoprotein receptor (LDLR) family has long been studied for its role in cholesterol transport and metabolism; however, the identification of apolipoprotein E4 (ApoE4), an LDLR ligand, as a genetic risk factor for late-onset Alzheimers disease (AD) has focused attention on the role this receptor family plays in the central nervous system (CNS). Surprisingly, it was discovered that two LDLR family members, Apolipoprotein E receptor 2 (Apoer2) and very-low-density lipoprotein receptor (Vldlr), play key roles in brain development and adult synaptic plasticity, primarily by mediating Reelin signaling...
March 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28285824/clasp2-links-reelin-to-the-cytoskeleton-during-neocortical-development
#9
Gregory M Dillon, William A Tyler, Kerilyn C Omuro, John Kambouris, Camila Tyminski, Shawna Henry, Tarik F Haydar, Uwe Beffert, Angela Ho
The Reelin signaling pathway plays a crucial role in regulating neocortical development. However, little is known about how Reelin controls the cytoskeleton during neuronal migration. Here, we identify CLASP2 as a key cytoskeletal effector in the Reelin signaling pathway. We demonstrate that CLASP2 has distinct roles during neocortical development regulating neuron production and controlling neuron migration, polarity, and morphogenesis. We found downregulation of CLASP2 in migrating neurons leads to mislocalized cells in deeper cortical layers, abnormal positioning of the centrosome-Golgi complex, and aberrant length/orientation of the leading process...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28284905/embryonic-mosaic-deletion-of-app-results-in-displaced-reelin-expressing-cells-in-the-cerebral-cortex
#10
D G Callahan, W M Taylor, M Tilearcio, T Cavanaugh, D J Selkoe, T L Young-Pearse
It is widely accepted that amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer's disease. In addition, APP has been proposed to have functions in numerous biological processes including neuronal proliferation, differentiation, migration, axon guidance, and neurite outgrowth, as well as in synapse formation and function. However, germline knockout of APP yields relatively subtle phenotypes, and brain development appears grossly normal. This is thought to be due in part to functional compensation by APP family members and other type I transmembrane proteins...
March 8, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28272509/optogenetic-control-of-the-dab1-signaling-pathway
#11
Liang Wang, Jonathan A Cooper
The Reelin-Dab1 signaling pathway regulates development of the mammalian brain, including neuron migrations in various brain regions, as well as learning and memory in adults. Extracellular Reelin binds to cell surface receptors and activates phosphorylation of the intracellular Dab1 protein. Dab1 is required for most effects of Reelin, but Dab1-independent pathways may contribute. Here we developed a single-component, photoactivatable Dab1 (opto-Dab1) by using the blue light-sensitive dimerization/oligomerization property of A...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255385/reelin-and-its-receptors-vldlr-and-apoer2-in-melanocytic-nevi
#12
A Mihail, G Coman, F Staniceanu, L Coman, S Zurac, O A Coman
Reelin is an extracellular signaling protein synthesized by Cajal-Retius cells in utero and early after birth, its presence being signaled in adult life too. Reelin acts on its receptors, VLDLR and ApoER2, acting on cytoskeleton, controlling migration and subsequently positioning and stabilizing the cortical neurons. We investigated the reelin presence and its receptors, VLDLR and ApoER2, in melanocytic nevi considering the neural crest origin of the nevus cells and their migration into skin during embrionary period...
January 2017: Journal of Medicine and Life
https://www.readbyqxmd.com/read/28229923/epigenetic-regulation-of-reln-and-gad1-in-the-frontal-cortex-fc-of-autism-spectrum-disorder-asd-subjects
#13
Adrian Zhubi, Ying Chen, Alessandro Guidotti, Dennis R Grayson
Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism that involves increases in the amounts of MECP2 binding to the corresponding promoters. In the current study, we examined the expression of RELN, GAD1, GAD2, and several other mRNAs implicated in this disorder in the frontal cortices (FC) of ASD and CON subjects. We also focused on the role that epigenetic processes play in the regulation of these genes in ASD brain...
February 13, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28213441/secreted-metalloproteinase-adamts-3-inactivates-reelin
#14
Himari Ogino, Arisa Hisanaga, Takao Kohno, Yuta Kondo, Kyoko Okumura, Takana Kamei, Tempei Sato, Hiroshi Asahara, Hitomi Tsuiji, Masaki Fukata, Mitsuharu Hattori
The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease; however, non-invasive methods that can upregulate Reelin activity in vivo have yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activity in vitro, but it remains controversial as to whether this effect occurs in vivo Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28210910/astrocyte-induced-reelin-expression-drives-proliferation-of-her2-breast-cancer-metastases
#15
Rahul Jandial, Cecilia Choy, Danielle M Levy, Mike Y Chen, Khairul I Ansari
Breast cancer metastasis to the brain develops after a clinical latency of years to even decades, suggesting that colonization of the brain is the most challenging step of the metastatic cascade. However, the underlying mechanisms used by breast cancer cells to successfully colonize the brain's microenvironment remain elusive. Reelin is an archetypal extracellular glycoprotein that regulates migration, proliferation, and lamination of neurons. It is epigenetically silenced in various cancers, and its expression in multiple myelomas is linked to poor patient survival...
February 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28206669/characterization-of-focal-cortical-dysplasia-with-balloon-cells-by-layer-specific-markers-evidence-for-differential-vulnerability-of-interneurons
#16
Julia M Nakagawa, Catharina Donkels, Susanne Fauser, Andreas Schulze-Bonhage, Marco Prinz, Josef Zentner, Carola A Haas
OBJECTIVE: Focal cortical dysplasia (FCD) is a major cause of pharmacoresistant focal epilepsy. Little is known about the pathomechanisms underlying the characteristic cytoarchitectural abnormalities associated with FCD. In the present study, a broad panel of markers identifying layer-specific neuron subpopulations was applied to characterize dyslamination and structural alterations in FCD with balloon cells (FCD 2b). METHODS: Pan-neuronal neuronal nuclei (NeuN) and layer-specific protein expression (Reelin, Calbindin, Calretinin, SMI32 (nonphosphorylated neurofilament H), Parvalbumin, transducin-like enhancer protein 4 (TLE4), and Vimentin) was studied by immunohistochemistry on paraffin sections of FCD2b cases (n = 22) and was compared to two control groups with (n = 7) or without epilepsy (n = 4 postmortem cases)...
April 2017: Epilepsia
https://www.readbyqxmd.com/read/28174271/reelin-transiently-promotes-n-cadherin-dependent-neuronal-adhesion-during-mouse-cortical-development
#17
Yuki Matsunaga, Mariko Noda, Hideki Murakawa, Kanehiro Hayashi, Arata Nagasaka, Seika Inoue, Takaki Miyata, Takashi Miura, Ken-Ichiro Kubo, Kazunori Nakajima
Reelin is an essential glycoprotein for the establishment of the highly organized six-layered structure of neurons of the mammalian neocortex. Although the role of Reelin in the control of neuronal migration has been extensively studied at the molecular level, the mechanisms underlying Reelin-dependent neuronal layer organization are not yet fully understood. In this study, we directly showed that Reelin promotes adhesion among dissociated neocortical neurons in culture. The Reelin-mediated neuronal aggregation occurs in an N-cadherin-dependent manner, both in vivo and in vitro...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28165338/the-chromatin-remodeling-factor-chd7-controls-cerebellar-development-by-regulating-reelin-expression
#18
Danielle E Whittaker, Kimberley L H Riegman, Sahrunizam Kasah, Conor Mohan, Tian Yu, Blanca Pijuan Sala, Husam Hebaishi, Angela Caruso, Ana Claudia Marques, Caterina Michetti, María Eugenia Sanz Smachetti, Apar Shah, Mara Sabbioni, Omer Kulhanci, Wee-Wei Tee, Danny Reinberg, Maria Luisa Scattoni, Holger Volk, Imelda McGonnell, Fiona C Wardle, Cathy Fernandes, M Albert Basson
The mechanisms underlying the neurodevelopmental deficits associated with CHARGE syndrome, which include cerebellar hypoplasia, developmental delay, coordination problems, and autistic features, have not been identified. CHARGE syndrome has been associated with mutations in the gene encoding the ATP-dependent chromatin remodeler CHD7. CHD7 is expressed in neural stem and progenitor cells, but its role in neurogenesis during brain development remains unknown. Here we have shown that deletion of Chd7 from cerebellar granule cell progenitors (GCps) results in reduced GCp proliferation, cerebellar hypoplasia, developmental delay, and motor deficits in mice...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28142128/the-clinical-phenotype-of-autosomal-dominant-lateral-temporal-lobe-epilepsy-related-to-reelin-mutations
#19
Roberto Michelucci, Patrizia Pulitano, Carlo Di Bonaventura, Simona Binelli, Concetta Luisi, Elena Pasini, Salvatore Striano, Pasquale Striano, Giangennaro Coppola, Angela La Neve, Anna Teresa Giallonardo, Oriano Mecarelli, Elena Serioli, Emanuela Dazzo, Manuela Fanciulli, Carlo Nobile
OBJECTIVE: To describe the clinical phenotype of 7 families with Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTE) related to Reelin (RELN) mutations comparing the data with those observed in 12 LGI1-mutated pedigrees belonging to our series. METHODS: Out of 40 Italian families with ADLTE, collected by epileptologists participating in a collaborative study of the Commission for Genetics of the Italian League against Epilepsy encompassing a 14-year period (2000-2014), 7 (17...
March 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28127196/construction-of-gpm6a-reelin-gfpcreert2-by-bac-recombination-using-a-specific-gene-in-hepatic-mesothelial-or-stellate-cells
#20
Hong-Bo Shi, Jin-Li Lou, Hong-Lin Shi, Feng Ren, Yu Chen, Zhong-Ping Duan
AIM: To prepare a Gpm6a/Reelin(GFPCreERT2) construct with a rapid and reliable strategy using a bacterial artificial chromosome (BAC). METHODS: Gpm6a and Reelin BACs were purified and transformed into SW102 E. coli by electroporation. The GFPCreERT2 fragment was prepared from a shuttle vector and transformed into SW102 E. coli carrying a BAC. Homologous recombination was induced in SW102 E. coli. Recombinant clones were screened and confirmed by PCR and restriction enzyme digestion...
January 14, 2017: World Journal of Gastroenterology: WJG
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