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https://www.readbyqxmd.com/read/28507985/control-of-neuronal-migration-and-aggregation-by-reelin-signaling-in-the-developing-cerebral-cortex
#1
REVIEW
Yuki Hirota, Kazunori Nakajima
The mammalian cerebral neocortex has a well-organized laminar structure, achieved by the highly coordinated control of neuronal migration. During cortical development, excitatory neurons born near the lateral ventricle migrate radially to reach their final positions to form the cortical plate. During this process, dynamic changes are observed in the morphologies and migration modes, including multipolar migration, locomotion, and terminal translocation, of the newborn neurons. Disruption of these migration processes can result in neuronal disorders such as lissencephaly and periventricular heterotopia...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28506622/meta-analyses-of-reln-variants-in-neuropsychiatric-disorders
#2
Na Chen, Yanping Bao, Yanxue Xue, Yan Sun, Die Hu, Shiqiu Meng, Lin Lu, Jie Shi
Reelin is a critical extracellular matrix glycoprotein and implicated in neurodevelopment and psychiatric disorders in animal model studies. The genetic polymorphism of RELN has also been reported to be associated with several psychiatric disorders, but the results remain controversial. Here, we conducted meta-analyses of RELN gene SNPs and related neuropsychiatric disorders (schizophrenia, autistic spectrum disorders, attention-deficit hyperactivity disorder, Alzheimer's disease and bipolar disorders). A total of 12 SNPs (rs736707, rs362691, rs607755, rs2229864, rs7341475, rs262355, rs362719, rs11496125, g...
May 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28498462/loss-of-reelin-suppresses-cell-survival-and-mobility-in-non-hodgkin-lymphoma
#3
Aixia Dou, Zhilun Wang, Ni Zhang, Junli Liu
Reelin, a secreted glycoprotein, was recently demonstrated to be involved in the pathogenesis of cancer. However, its oncogenic activities in non-Hodgkin lymphoma (NHL) remain unclear. Therefore, we aimed to evaluate the functional role of reelin in NHL, and the underlying molecular mechanisms. In the present study, we analyzed reelin expression in lymphoma tissues and cell lines using immunohistochemistry, immunofluorescence staining, qRT-PCR and western blotting. Then, the expression of Reelin was silenced with short hairpin RNA (shRNA)-expressing plasmid in the NHL cell line A20...
May 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28495490/further-evidence-for-the-association-between-lrp8-and-schizophrenia
#4
Xiao Xiao, Hao Yu, Jun Li, Lu Wang, Lingyi Li, Hong Chang, Dai Zhang, Weihua Yue, Ming Li
Previous studies (including genome-wide association study (GWAS) and candidate gene studies) have revealed the important roles of genetic risk factors in schizophrenia, and RELN has been identified as a risk gene for this illness. We recently found that the low-density lipoprotein receptor-related protein 8 (LRP8), a receptor of Reelin (the protein encoded by RELN), was significantly associated with schizophrenia and bipolar disorder in European populations. To further enhance our understanding of its role in the risk of psychiatric illnesses, we conducted meta-analyses of a higher density of single nucleotide polymorphisms (SNPs, N=173) in LRP8 to understand their associations with schizophrenia in much larger samples (39,400 cases and 50,357 controls) from populations of European, Chinese and African American ancestries...
May 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28495474/late-effect-of-developmental-exposure-to-glycidol-on-hippocampal-neurogenesis-in-mice-loss-of-parvalbumin-expressing-interneurons
#5
Masashi Kawashima, Yousuke Watanabe, Kota Nakajima, Hirotada Murayama, Rei Nagahara, Meilan Jin, Toshinori Yoshida, Makoto Shibutani
Developmental exposure to glycidol of rats causes axonal injury targeting axon terminals in dams and transient disruption of late-stage differentiation of hippocampal neurogenesis, accompanying sustained increase in the number of reelin-producing or calretinin-expressing interneurons in offspring. The molecular mechanism of disruptive neurogenesis probably targets the newly generating nerve terminals. We previously found differences between mice and rats in the effects on hippocampal neurogenesis after developmental exposure to the same neurotoxic substances...
May 8, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28484035/intersectin-1-is-a-component-of-the-reelin-pathway-to-regulate-neuronal-migration-and-synaptic-plasticity-in-the-hippocampus
#6
Burkhard Jakob, Gaga Kochlamazashvili, Maria Jäpel, Aziz Gauhar, Hans H Bock, Tanja Maritzen, Volker Haucke
Brain development and function depend on the directed and coordinated migration of neurons from proliferative zones to their final position. The secreted glycoprotein Reelin is an important factor directing neuronal migration. Loss of Reelin function results in the severe developmental disorder lissencephaly and is associated with neurological diseases in humans. Reelin signals via the lipoprotein receptors very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), but the exact mechanism by which these receptors control cellular function is poorly understood...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28472243/the-subpial-granular-layer-and-transient-versus-persisting-cajal-retzius-neurons-of-the-fetal-human-cortex
#7
Gundela Meyer, Miriam González-Gómez
Neurons of the subpial granular layer (SGL) in the human marginal zone (MZ) migrate tangentially from the periolfactory subventricular zone all over the neocortex. After an immature stage, from 14 to 18 gestational weeks (GW), the SGL attains maximum prominence around midgestation. At 20-25 GW, a transient miniature cell type in the MZ expresses glutamate decarboxylase (GAD) and calretinin, and extends a varicose plexus surrounding somata of large transient Cajal-Retzius neurons (tCRN), potentially modulating their activity...
May 4, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28446613/structural-basis-for-ligand-capture-and-release-by-the-endocytic-receptor-apoer2
#8
Hidenori Hirai, Norihisa Yasui, Keitaro Yamashita, Sanae Tabata, Masaki Yamamoto, Junichi Takagi, Terukazu Nogi
Apolipoprotein E receptor 2 (ApoER2) is a close homologue of low-density lipoprotein receptor (LDLR) that mediates the endocytosis of ligands, including LDL particles. LDLR family members have been presumed to explore a large conformational space to capture ligands in the extended conformation at the cell surface. Ligands are subsequently released through a pH-titrated structural transition to a self-docked, contracted-closed conformation. In addition to lipoprotein uptake, ApoER2 is implicated in signal transduction during brain development through capture of the extracellular protein reelin...
April 26, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28433501/disrupted-in-schizophrenia-1-regulates-the-processing-of-reelin-in-the-perinatal-cortex
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
April 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28272509/optogenetic-control-of-the-dab1-signaling-pathway
#19
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
#20
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
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