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https://www.readbyqxmd.com/read/29770645/atoh1-regulation-in-the-cochlea-more-than-just-transcription
#1
REVIEW
Yen-Fu Cheng
More than 80% of all cases of deafness are related to the death or degeneration of cochlear hair cells and the associated spiral ganglion neurons, and a lack of regeneration of these cells leads to permanent hearing loss. Therefore, the regeneration of lost hair cells is an important goal for the treatment of deafness. Atoh1 is a basic helix-loop-helix (bHLH) transcription factor that is critical in both the development and regeneration of cochlear hair cells. Atoh1 is transcriptionally regulated by several signaling pathways, including Notch and Wnt signalings...
July 13, 2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29768179/intestinal-epithelial-wnt-signaling-mediates-acetylcholine-triggered-host-defense-against-infection
#2
Sid Ahmed Labed, Khursheed A Wani, Sakthimala Jagadeesan, Abdul Hakkim, Mehran Najibi, Javier Elbio Irazoqui
Regulated antimicrobial peptide expression in the intestinal epithelium is key to defense against infection and to microbiota homeostasis. Understanding the mechanisms that regulate such expression is necessary for understanding immune homeostasis and inflammatory disease and for developing safe and effective therapies. We used Caenorhabditis elegans in a preclinical approach to discover mechanisms of antimicrobial gene expression control in the intestinal epithelium. We found an unexpected role for the cholinergic nervous system...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29768168/a-worm-s-gut-feelings-neuronal-muscarinic-and-epithelial-canonical-wnt-pathways-promote-antimicrobial-defense
#3
Romana R Gerner, Manuela Raffatellu
Molecular mechanisms connecting the gut-brain axis to immunity remain elusive. In this issue of Immunity, Labed et al. (2018) demonstrate that two evolutionarily conserved signaling mechanisms, the neuronal muscarinic and the epithelial Wnt pathways, together induce antimicrobial peptide expression that protects Caenorhabditis elegans against intestinal infection.
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29752762/feeding-and-glp-1-receptor-activation-stabilize-%C3%AE-catenin-in-specific-hypothalamic-nuclei-in-male-rats
#4
Hayden J L McEwen, Emmanuelle Cognard, Sharon R Ladyman, Zin Khant-Aung, Alexander Tups, Peter R Shepherd, David R Grattan
β-catenin is a multifunctional protein that can act in the canonical Wnt/β-catenin pathway to regulate gene expression but can also bind to cadherin proteins in adherens junctions where it plays a key role in regulating cytoskeleton linked with these junctions. Recently, evidence has been presented indicating an essential role for β-catenin in regulating trafficking of insulin vesicles in β-cells and showing that changes in nutrient levels rapidly alter levels of β-catenin in these cells. Given the importance of neuroendocrine hormone secretion in the regulation of whole body glucose homeostasis, the objective of this study was to investigate whether β-catenin signalling is regulated in the hypothalamus during the normal physiological response to food intake...
May 11, 2018: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29751817/tcf7l2-is-essential-for-neurogenesis-in-the-developing-mouse-neocortex
#5
Olga Chodelkova, Jan Masek, Vladimir Korinek, Zbynek Kozmik, Ondrej Machon
Generation of neurons in the embryonic neocortex is a balanced process of proliferation and differentiation of neuronal progenitor cells. Canonical Wnt signalling is crucial for expansion of radial glial cells in the ventricular zone and for differentiation of intermediate progenitors in the subventricular zone. We detected abundant expression of two transcrtiption factors mediating canonical Wnt signalling, Tcf7L1 and Tcf7L2, in the ventricular zone of the embryonic neocortex. Conditional knock-out analysis showed that Tcf7L2, but not Tcf7L1, is the principal Wnt mediator important for maintenance of progenitor cell identity in the ventricular zone...
May 11, 2018: Neural Development
https://www.readbyqxmd.com/read/29751779/essential-role-of-atp6ap2-enrichment-in-caveolae-lipid-raft-microdomains-for-the-induction-of-neuronal-differentiation-of-stem-cells
#6
Nehman Makdissy, Katia Haddad, Jeanne D'arc AlBacha, Diana Chaker, Bassel Ismail, Albert Azar, Ghada Oreibi, David Ayoub, Ibrahim Achkar, Didier Quilliot, Ziad Fajloun
BACKGROUND: The subcellular distribution of prorenin receptor and adaptor protein ATP6AP2 may affect neurogenesis. In this study, we hypothesized that ATP6AP2 expression and subcellular relocalization from caveolae/lipid raft microdomains (CLR-Ms) to intracellular sites may correlate with neuronal differentiation (Neu-Dif) of adipose-derived mesenchymal stem cells (ADSCs). METHODS: Human ADSCs isolated from 24 healthy donors and 24 patients with neurological disorders (ND) were cultured and induced for Neu-Dif...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29737454/targeting-%C3%AE-catenin-in-glast-expressing-cells-impact-on-anxiety-and-depression-related-behavior-and-hippocampal-proliferation
#7
Rebeca Vidal, Emilio Garro-Martínez, Álvaro Díaz, Elena Castro, Eva Florensa-Zanuy, Makoto M Taketo, Ángel Pazos, Fuencisla Pilar-Cuéllar
β-catenin (key mediator in the Wnt signaling pathway) contributes to the pathophysiology of mood disorders, associated to neurogenesis and neuroplasticity. Decreased β-catenin protein levels have been observed in the hippocampus and prefrontal cortex of depressed subjects. Additionally, the antidepressants exert, at least in part, their neurogenic effects by increasing β-catenin levels in the subgranular zone of the hippocampus. To further understand the role of β-catenin in depression and anxiety, we generated two conditional transgenic mice in which β-catenin was either inactivated or stabilized in cells expressing CreERT under the control of the astrocyte-specific glutamate transporter (GLAST) promoter inducible by tamoxifen, which presents high expression levels on the subgranular zone of the hippocampus...
May 8, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29705802/salidroside-protection-against-oxidative-stress-injury-through-the-wnt-%C3%AE-catenin-signaling-pathway-in-rats-with-parkinson-s-disease
#8
Dong-Mei Wu, Xin-Rui Han, Xin Wen, Shan Wang, Shao-Hua Fan, Juan Zhuang, Yong-Jian Wang, Zi-Feng Zhang, Meng-Qiu Li, Bin Hu, Qun Shan, Chun-Hui Sun, Jun Lu, Yuan-Lin Zheng
BACKGROUND/AIMS: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism. METHODS: SDS and LiCl (activators of the Wnt/β-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/β-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo...
April 25, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29684334/the-mkk7-inhibitor-peptide-gadd45%C3%AE-i-attenuates-er-stress-induced-mitochondrial-dysfunction-in-ht22-cells-involvement-of-jnk-wnt-pathway
#9
Guang-Hua Xu, Bing-Jun Song, Dan Liu, Yu-Hua Chen, Yuan Zhou, Wen-Bo Liu, Hua Li, Tian-Lin Long, Rui Zhang, Wei Liu
JNK, a member of the mitogen activated protein kinases (MAPKs) superfamily, plays a key role in cell death in many neurological disorders, but systemic inhibition of JNK has detrimental side effects. JNK can be regulated by two direct upstream kinases: MAPK kinase 4 (MKK4) and MAPK kinase 7 (MKK7). Here, we investigated the effect of GADD45β-I, a recently designed cell-permeable inhibitor peptide for MKK7, on endoplasmic reticulum (ER) stress-induced cytotoxicity in neuronal HT22 cells. We found that treatment with the ER stress inducer tunicamycin (TM) increased the phosphorylation of JNK and MKK7 in HT22 cells, which was nullified by GADD45β-I...
April 20, 2018: Brain Research
https://www.readbyqxmd.com/read/29673481/cell-autonomous-regulation-of-dendrite-self-avoidance-by-the-wnt-secretory-factor-mig-14-wntless
#10
Chien-Po Liao, Hsun Li, Hsiu-Hsiang Lee, Cheng-Ting Chien, Chun-Liang Pan
Self-avoidance allows sister dendrites from the same neuron to form non-redundant coverage of the sensory territory and is important for neural circuitry functions. Here, we report an unexpected, cell-autonomous role of the Wnt-secretory factor MIG-14/Wntless in mediating dendrite self-avoidance in the C. elegans multidendritic PVD neurons. Similar findings in Drosophila suggest that this novel function of Wntless is conserved. The mig-14 mutant shows defects in dendrite self-avoidance, and ectopic MIG-14 expression triggers dendrite repulsion...
April 18, 2018: Neuron
https://www.readbyqxmd.com/read/29660932/neuroprotective-effects-of-ferruginol-jatrophone-and-junicedric-acid-against-amyloid-%C3%AE-injury-in-hippocampal-neurons
#11
Juan M Zolezzi, Carolina B Lindsay, Felipe G Serrano, Roxana C Ureta, Cristina Theoduloz, Guillermo Schmeda-Hirschmann, Nibaldo C Inestrosa
Soluble amyloid-β (Aβ) oligomers have been recognized as early neurotoxic intermediates with a key role in the synaptic dysfunction observed in Alzheimer's disease (AD). Aβ oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Additionally, the presence of Aβ oligomers is associated with imbalanced intracellular calcium levels and apoptosis in neurons. In this context, we evaluated the effects of three diterpenes (ferruginol, jatrophone, and junicedric acid) that are found in medicinal plants and have several forms of biological activity...
April 10, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29659741/formin-2-regulates-lysosomal-degradation-of-wnt-associated-%C3%AE-catenin-in-neural-progenitors
#12
Gewei Lian, Anjen Chenn, Victor Ekuta, Sneha Kanaujia, Volney Sheen
Although neural progenitor proliferation along the ventricular zone is regulated by β-catenin through Wnt signaling, the cytoskeletal mechanisms that regulate expression and localization of these proteins are not well understood. Our prior studies have shown that loss of the actin-binding Filamin A (FlnA) and actin-nucleating protein Formin 2 (Fmn2) impairs endocytosis of low-density-lipoprotein-receptor-related protein 6 (Lrp6), thereby disrupting β-catenin activation, resulting in decreased brain size. Here, we report that activated RhoA-GTPase disengages Fmn2 N- to C-terminal binding to promote Fmn2 activation and redistribution into lysosomal vesicles...
April 5, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29659554/demyelination-in-multiple-sclerosis-reprogramming-energy-metabolism-and-potential-ppar%C3%AE-agonist-treatment-approaches
#13
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Demyelination in multiple sclerosis (MS) cells is the site of several energy metabolic abnormalities driven by dysregulation between the opposed interplay of peroxisome proliferator-activated receptor γ (PPARγ) and WNT/β-catenin pathways. We focus our review on the opposing interactions observed in demyelinating processes in MS between the canonical WNT/β-catenin pathway and PPARγ and their reprogramming energy metabolism implications. Demyelination in MS is associated with chronic inflammation, which is itself associated with the release of cytokines by CD4⁺ Th17 cells, and downregulation of PPARγ expression leading to the upregulation of the WNT/β-catenin pathway...
April 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29658475/-aerobic-glycolysis-activation-through-canonical-wnt-%C3%AE-catenin-pathway-in-als
#14
Alexandre Vallée
Energy is the major determinant of neuronal viability. We focus our synthesis on the hypothesis of the development of aerobic glycolysis by the stimulation of the canonical WNT/β-catenin pathway in amyotrophic lateral sclerosis (ALS). The stimulation of the canonical WNT/β-catenin pathway induces the activation of aerobic glycolysis, also called Warburg effect, via the stimulation of glycolytic enzymes such as Glut (glucose transporter), PKM2 (pyruvate kinase M2), PDK1 (pyruvate dehydrogenase kinase 1), LDH-A (lactate dehydrogenase A) and MCT-1 (monocarboxylate transporter 1)...
April 2018: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29650976/wnt-signal-activation-induces-midbrain-specification-through-direct-binding-of-the-beta-catenin-tcf4-complex-to-the-en1-promoter-in-human-pluripotent-stem-cells
#15
Ji Young Kim, Jae Souk Lee, Hyun Sub Hwang, Dongjin R Lee, Chul-Yong Park, Sung Jun Jung, Young Rang You, Dae-Sung Kim, Dong-Wook Kim
The canonical Wnt signal pathway plays a pivotal role in anteroposterior patterning and midbrain specification during early neurogenesis. Activating Wnt signal has been a strategy for differentiating human pluripotent stem cells (PSCs) into midbrain dopaminergic (DA) neurons; however, the underlying molecular mechanism(s) of how the Wnt signal drives posterior fate remained unclear. In this study, we found that activating the canonical Wnt signal significantly upregulated the expression of EN1, a midbrain-specific marker, in a fibroblast growth factor signal-dependent manner in human PSC-derived neural precursor cells (NPCs)...
April 13, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29643768/mirna-431-prevents-amyloid-%C3%AE-induced-synapse-loss-in-neuronal-cell-culture-model-of-alzheimer-s-disease-by-silencing-kremen1
#16
Sean P Ross, Kelly E Baker, Amanda Fisher, Lee Hoff, Elena S Pak, Alexander K Murashov
Synapse loss is well regarded as the underlying cause for the progressive decline of memory function over the course of Alzheimer's disease (AD) development. Recent observations suggest that the accumulation of the Wnt antagonist Dickkopf-1 (Dkk1) in the AD brain plays a critical role in triggering synaptic degeneration. Mechanistically, Dkk1 cooperates with Kremen1 (Krm1), its transmembrane receptor, to block the Wnt/β-catenin signaling pathway. Here, we show that silencing Krm1 with miR-431 prevents amyloid-β-mediated synapse loss in cortico-hippocampal cultures isolated from triple transgenic 3xTg-AD mice...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29643329/shared-effects-of-disc1-disruption-and-elevated-wnt-signaling-in-human-cerebral-organoids
#17
Priya Srikanth, Valentina N Lagomarsino, Christina R Muratore, Steven C Ryu, Amy He, Walter M Taylor, Constance Zhou, Marlise Arellano, Tracy L Young-Pearse
The development of three-dimensional culture methods has allowed for the study of developing cortical morphology in human cells. This provides a new tool to study the neurodevelopmental consequences of disease-associated mutations. Here, we study the effects of isogenic DISC1 mutation in cerebral organoids. DISC1 has been implicated in psychiatric disease based on genetic studies, including its interruption by a balanced translocation that increases the risk of major mental illness. Isogenic wild-type and DISC1-disrupted human-induced pluripotent stem cells were used to generate cerebral organoids, which were then examined for morphology and gene expression...
April 12, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29642895/wnt3a-ligand-facilitates-autophagy-in-hippocampal-neurons-by-modulating-a-novel-gsk-3%C3%AE-ampk-axis
#18
Juvenal A Ríos, Juan A Godoy, Nibaldo C Inestrosa
BACKGROUND: In the adult central nervous system (CNS), Wnt signaling regulates dendritic structure and synaptic plasticity. The Wnt signaling pathway can be divided into the canonical (β-catenin-dependent) and non-canonical pathways. In the canonical pathway, the binding of canonical ligands such as Wnt3a to the Frizzled receptor induces inactivation of glycogen synthase kinase-3β (GSK-3β), which stabilizes β-catenin and allows its translocation to the nucleus. However, to date, few studies have focused on β-catenin-independent Wnt signaling or explained the underlying mechanisms connecting Wnt signaling to cellular energy metabolism...
April 11, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29614674/optical-depolarization-of-dcx-expressing-cells-promoted-cognitive-recovery-and-maturation-of-newborn-neurons-via-the-wnt-%C3%AE-catenin-pathway
#19
Ming-Liang Zhao, Shi-Jin Chen, Xiao-Hong Li, Li-Na Wang, Feng Chen, Shi-Jiang Zhong, Cheng Yang, Sheng-Kai Sun, Jian-Jun Li, Hua-Jiang Dong, Yue-Qing Dong, Yi Wang, Chong Chen
Electrical excitability by membrane depolarization is crucial for survival and maturation of newborn cells in the dentate gyrus of the hippocampus. However, traditional technology for membrane depolarization lacks temporal and spatial precision. Optogenetics can be used to activate channelrhodopsin-2 (ChR2), allowing cationic current to depolarize genetically targeted cells. In this study, we used ChR2-EGFP driven by doublecortin (DCX) to promote survival and maturation of newborn cells in the dentate gyrus after traumatic brain injury (TBI)...
March 28, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29602811/identification-of-proteins-required-for-precise-positioning-of-apc2-in-dendrites
#20
Alexis T Weiner, Dylan Y Seebold, Nick L Michael, Michelle Guignet, Chengye Feng, Brandon Follick, Brandon A Yusko, Nathan P Wasilko, Pedro Torres-Gutierrez, Melissa M Rolls
In Drosophila neurons, uniform minus-end-out polarity in dendrites is maintained in part by kinesin-2-mediated steering of growing microtubules at branch points. Apc links the kinesin motor to growing microtubule plus ends and Apc2 recruits Apc to branch points where it functions. Because Apc2 acts to concentrate other steering proteins to branch points, we wished to understand how Apc2 is targeted. From an initial broad candidate RNAi screen, we found Miro (a mitochondrial transport protein), Ank2, Axin, spastin and Rac1 were required to position Apc2-GFP at dendrite branch points...
March 30, 2018: G3: Genes—Genomes—Genetics
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