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https://www.readbyqxmd.com/read/28329675/trimethylation-and-acetylation-of-%C3%AE-catenin-at-lysine-49-represent-key-elements-in-esc-pluripotency
#1
Katrin Hoffmeyer, Dirk Junghans, Benoit Kanzler, Rolf Kemler
Wnt/β-catenin signaling is required for embryonic stem cell (ESC) pluripotency by inducing mesodermal differentiation and inhibiting neuronal differentiation; however, how β-catenin counter-regulates these differentiation pathways is unknown. Here, we show that lysine 49 (K49) of β-catenin is trimethylated (β-catMe3) by Ezh2 or acetylated (β-catAc) by Cbp. Significantly, β-catMe3 acts as a transcriptional co-repressor of the neuronal differentiation genes sox1 and sox3, whereas β-catAc acts as a transcriptional co-activator of the key mesodermal differentiation gene t-brachyury (t-bra)...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28321286/crispr-cas9-mediated-heterozygous-knockout-of-the-autism-gene-chd8-and-characterization-of-its-transcriptional-networks-in-cerebral-organoids-derived-from-ips-cells
#2
Ping Wang, Ryan Mokhtari, Erika Pedrosa, Michael Kirschenbaum, Can Bayrak, Deyou Zheng, Herbert M Lachman
BACKGROUND: CHD8 (chromodomain helicase DNA-binding protein 8), which codes for a member of the CHD family of ATP-dependent chromatin-remodeling factors, is one of the most commonly mutated genes in autism spectrum disorders (ASD) identified in exome-sequencing studies. Loss of function mutations in the gene have also been found in schizophrenia (SZ) and intellectual disabilities and influence cancer cell proliferation. We previously reported an RNA-seq analysis carried out on neural progenitor cells (NPCs) and monolayer neurons derived from induced pluripotent stem (iPS) cells that were heterozygous for CHD8 knockout (KO) alleles generated using CRISPR-Cas9 gene editing...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28321181/rnf146-inhibits-excessive-autophagy-by-modulating-the-wnt-%C3%AE-catenin-pathway-in-glutamate-excitotoxicity-injury
#3
Yuefan Yang, Peng Luo, Haoxiang Xu, Shuhui Dai, Wei Rao, Cheng Peng, Wenke Ma, Jiu Wang, Hongyu Xu, Lei Zhang, Sai Zhang, Zhou Fei
Glutamate induced excitotoxicity is common in diverse neurological disorders. RNF146 as an E3 ubiquitin ligase protects neurons against excitotoxicity via interfering with Poly (ADP-ribose) (PAR) polymer-induced cell death (parthanatos). However, the neuroprotective role of RNF146 has not been fully understood. We aimed to investigate the role of RNF146 in modulating autophagy in HT22 cells under glutamate excitotoxicity injury. Here we found that induction of RNF146 decreased the cellular damage and excitotoxicity induced by glutamate...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28265002/deletion-of-pofut1-in-mouse-skeletal-myofibers-induces-muscle-aging-related-phenotypes-in-cis-and-in-trans
#4
Deborah A Zygmunt, Neha Singhal, Mi-Lyang Kim, Megan L Cramer, Kelly E Crowe, Rui Xu, Ying Jia, Jessica Adair, Isabel Martinez-Pena Y Valenzuela, Mohammed Akaaboune, Peter White, Paulus M Janssen, Paul T Martin
Sarcopenia, the loss of muscle mass and strength during normal aging, involves coordinate changes in skeletal myofibers and the cells that contact them, including satellite cells and motor neurons. Here we show that Protein O-fucosyltransferase 1 (Pofut1), a gene that encodes a glycosyltransferase required for NotchR-mediated cell-cell signaling, has reduced expression in aging skeletal muscle. Moreover, premature postnatal deletion of Pofut1 in skeletal myofibers can induce aging-related phenotypes in cis within skeletal myofibers and in trans within satellite cells and within motor neurons via the neuromuscular junction...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28261092/screening-for-small-molecule-inhibitors-of-statin-induced-app-c-terminal-toxic-fragment-production
#5
Karen S Poksay, Douglas J Sheffler, Patricia Spilman, Jesus Campagna, Barbara Jagodzinska, Olivier Descamps, Olivia Gorostiza, Alex Matalis, Michael Mullenix, Dale E Bredesen, Nicholas D P Cosford, Varghese John
Alzheimer's disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss is the intracellular caspase cleavage of the amyloid precursor protein (APP) resulting in release of the toxic C-terminal 31-amino acid peptide APP-C31 along with the production of APPΔC31, full-length APP minus the C-terminal 31 amino acids. We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28244619/sfrp2-enhanced-the-adipogenic-and-neuronal-differentiation-potentials-of-stem-cells-from-apical-papilla
#6
Xiao Lin, Rui Dong, ShuDiao Hao, Guoxia Yu, Liping Wang, Jun Li, Zhipeng Fan
Dental tissue-derived mesenchymal stem cells (MSCs) are easily obtained and considered as a favorable cell source for tissue engineering, but the regulation of direct differentiation is unknown which restricts their application. The present study investigated the effect of SFRP2, a WNT signaling modulator, on MSC differentiation using stem cells from apical papilla (SCAPs). The cells were cultured in specific inducing medium for adipogenic, neurogenic, or chondrogenic differentiation. Over-expression of SFRP2 via lentiviral infection enhanced the adipogenic and neurogenic differentiation of SCAPs...
February 28, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28241900/expression-of-protocadherin-11yb-pcdh11yb-in-seminal-germ-cells-is-correlated-with-fertility-status-in-men
#7
Thottathil R Anilkumar, Anandavalli N Devi, Sathy M Pillai, Krishnapillai Jayakrishnan, Oommen V Oommen, Pradeep G Kumar
Protocadherin 11 Y-linked (PCDH11Y), a member of the cadherin superfamily, is predominantly expressed in the central nervous system, is encoded by the Yp11.2 locus and exists in three isoforms: 11Ya, 11Yb and 11Yc. PCDH11Y is upregulated by retinoic acid signalling and is essential for spermatogonial differentiation and initiation of meiosis. PCDH11Y mediates Wnt signalling, which plays a crucial role in the differentiation of various cell types. PCDH11Y has been implicated in neuronal cell differentiation and proliferation, but its association with spermatogenesis has not yet been addressed...
February 28, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28240680/inhibition-of-wnt-signaling-reduces-differentiation-and-induces-sensitivity-to-doxorubicin-in-human-malignant-neuroblastoma-sh-sy5y-cells
#8
Junjira Suebsoonthron, Thiranut Jaroonwitchawan, Montarop Yamabhai, Parinya Noisa
Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative for a better treatment. WNT signaling plays significant roles in the survival, proliferation, and differentiation of human neuroblastoma. In this report, WNT signaling of a malignant human neuroblastoma cell line, SH-SY5Y cells, was inhibited by XAV939, a specific inhibitor of the Tankyrase enzyme...
February 24, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28222310/circulating-mirna-associated-with-posttraumatic-stress-disorder-in-a-cohort-of-military-combat-veterans
#9
Christiana G Martin, Hyungsuk Kim, Sijung Yun, Whitney Livingston, Joseph Fetta, Vincent Mysliwiec, Tristin Baxter, Jessica M Gill
Posttraumatic stress disorder (PTSD) affects many returning combat veterans, but underlying biological mechanisms remain unclear. In order to compare circulating micro RNA (miRNA) of combat veterans with and without PTSD, peripheral blood from 24 subjects was collected following deployment, and isolated miRNA was sequenced. PTSD was associated with 8 differentially expressed miRNA. Pathway analysis shows that PTSD is related to the axon guidance and Wnt signaling pathways, which work together to support neuronal development through regulation of growth cones...
January 31, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28219675/tcf7l2-plays-crucial-roles-in-forebrain-development-through-regulation-of-thalamic-and-habenular-neuron-identity-and-connectivity
#10
Myungsin Lee, Jiyeon Yoon, Hobeom Song, Bumwhee Lee, Duc Tri Lam, Jaeseung Yoon, Kwanghee Baek, Hans Clevers, Yongsu Jeong
The thalamus acts as a central integrator for processing and relaying sensory and motor information to and from the cerebral cortex, and the habenula plays pivotal roles in emotive decision making by modulating dopaminergic and serotonergic circuits. These neural compartments are derived from a common developmental progenitor domain, called prosomere 2, in the caudal forebrain. Thalamic and habenular neurons exhibit distinct molecular profile, neurochemical identity, and axonal circuitry. However, the mechanisms of how their progenitors in prosomere 2 give rise to these two populations of neurons and contribute to the forebrain circuitry remains unclear...
April 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28205531/wnt5a-is-a-crucial-regulator-of-neurogenesis-during-cerebellum-development
#11
Chandramohan Subashini, Sivadasan Bindu Dhanesh, Chih-Ming Chen, Paul Ann Riya, Vadakkath Meera, Thulasi Sheela Divya, Rejji Kuruvilla, Kerstin Buttler, Jackson James
The role of Wnt5a has been extensively explored in various aspects of development but its role in cerebellar development remains elusive. Here, for the first time we unravel the expression pattern and functional significance of Wnt5a in cerebellar development using Wnt5a(-/-) and Nestin-Cre mediated conditional knockout mouse models. We demonstrate that loss of Wnt5a results in cerebellar hypoplasia and depletion of GABAergic and glutamatergic neurons. Besides, Purkinje cells of the mutants displayed stunted, poorly branched dendritic arbors...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195124/pervasive-translational-regulation-of-the-cell-signalling-circuitry-underlies-mammalian-development
#12
Kotaro Fujii, Zhen Shi, Olena Zhulyn, Nicolas Denans, Maria Barna
The degree and dynamics of translational control during mammalian development remain poorly understood. Here we monitored translation of the mammalian genome as cells become specified and organize into tissues in vivo. This identified unexpected and pervasive translational regulation of most of the core signalling circuitry including Shh, Wnt, Hippo, PI3K and MAPK pathways. We further identify and functionally characterize a complex landscape of upstream open reading frames (uORFs) across 5'-untranslated regions (UTRs) of key signalling components...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28195036/gsk-3%C3%AE-inhibition-induced-neuroprotection-regeneration-and-functional-recovery-after-intracerebral-hemorrhagic-stroke
#13
Yingying Zhao, Zheng Zachory Wei, James Ya Zhang, Yongbo Zhang, Soonmi Won, Jinmei Sun, Shan Ping Yu, Jimei Li, Ling Wei
Hemorrhagic stroke is a devastating disease that lacks effective therapies. In the present investigation, we tested 6-bromoindirubin-3'-oxime (BIO) as a selective glycogen synthase kinase-3β (GSK-3β) inhibitor in a mouse model of intracerebral hemorrhage (ICH). ICH was induced by injection of collagenase IV into the striatum of 8 to 10-week old C57BL/6 mice. BIO (8 µg/kg, i.p.) was administered following either an acute delivery (0 - 2 hr delay) or a prolonged regimen (every 48 hrs starting at 3 days postICH)...
February 14, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28187790/retinoic-acid-and-tgf-%C3%AE-signalling-cooperate-to-overcome-mycn-induced-retinoid-resistance
#14
David J Duffy, Aleksandar Krstic, Melinda Halasz, Thomas Schwarzl, Anja Konietzny, Kristiina Iljin, Desmond G Higgins, Walter Kolch
BACKGROUND: Retinoid therapy is widely employed in clinical oncology to differentiate malignant cells into their more benign counterparts. However, certain high-risk cohorts, such as patients with MYCN-amplified neuroblastoma, are innately resistant to retinoid therapy. Therefore, we employed a precision medicine approach to globally profile the retinoid signalling response and to determine how an excess of cellular MYCN antagonises these signalling events to prevent differentiation and confer resistance...
February 10, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28179206/recombinant-insulin-like-growth-factor-binding-protein-4-inhibits-proliferation-and-promotes-differentiation-of-neural-progenitor-cells
#15
Hanxu Niu, Rongbin Gou, Qunyuan Xu, Deyi Duan
Insulin-like growth factor (IGF) is involved in regulating many processes during neural development, and IGF binding protein-4 (IGFBP4) functions as a modulator of IGF actions or in an IGF-independent manner (e.g., via inhibiting Wnt/β-catenin signaling). In the present study, neural progenitor cells (NPCs) were isolated from the forebrain of newborn mice to investigate effects of IGFBP4 on the proliferation and differentiation of NPCs. The proliferation of NPCs was evaluated using Cell Counting Kit-8 (CCK-8) after treatment with or without IGFBP4 as well as blockers of IGF-IR and β-catenin...
March 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28154134/cdon-deficiency-causes-cardiac-remodeling-through-hyperactivation-of-wnt-%C3%AE-catenin-signaling
#16
Myong-Ho Jeong, Hyun-Ji Kim, Jung-Hoon Pyun, Kyu-Sil Choi, Dong I Lee, Soroosh Solhjoo, Brian O'Rourke, Gordon F Tomaselli, Dong Seop Jeong, Hana Cho, Jong-Sun Kang
On pathological stress, Wnt signaling is reactivated and induces genes associated with cardiac remodeling and fibrosis. We have previously shown that a cell surface receptor Cdon (cell-adhesion associated, oncogene regulated) suppresses Wnt signaling to promote neuronal differentiation however its role in heart is unknown. Here, we demonstrate a critical role of Cdon in cardiac function and remodeling. Cdon is expressed and predominantly localized at intercalated disk in both mouse and human hearts. Cdon-deficient mice develop cardiac dysfunction including reduced ejection fraction and ECG abnormalities...
February 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28142224/effects-of-sulforaphane-on-neural-stem-cell-proliferation-and-differentiation
#17
Zhenxian Han, Qian Xu, Changfu Li, Hong Zhao
Sulforaphane (SFN) is a natural organosulfur compound with anti-oxidant and anti-inflammation properties. The objective of this study is to investigate the effect of SFN on the proliferation and differentiation of neural stem cells (NSC). NSCs were exposed to SFN at the concentrations ranging from 0.25 to 10 µM. Cell viability was evaluated with MTT assay and lactate dehydogenase (LDH) release assay. The proliferation of NSCs was evaluated with neurosphere formation assay and Ki-67 staining. The level of Tuj-1 was evaluated with immunostaining and Western blot to assess NSC neuronal differentiation...
January 31, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28137846/endothelial-wnt-%C3%AE-catenin-signaling-reduces-immune-cell-infiltration-in-multiple-sclerosis
#18
Justin E Lengfeld, Sarah E Lutz, Julian R Smith, Claudiu Diaconu, Cameron Scott, Sigal B Kofman, Claire Choi, Craig M Walsh, Cedric S Raine, Ilir Agalliu, Dritan Agalliu
Disruption of the blood-brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis. Although wingless integrated MMTV (Wnt)/β-catenin signaling plays an essential role in BBB formation and maintenance in healthy CNS, its role in BBB repair in neurologic diseases such as MS remains unclear...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28134846/neurogenic-traditional-chinese-medicine-as-a-promising-strategy-for-the-treatment-of-alzheimer-s-disease
#19
REVIEW
Sravan Gopalkrishnashetty Sreenivasmurthy, Jing-Yi Liu, Ju-Xian Song, Chuan-Bin Yang, Sandeep Malampati, Zi-Ying Wang, Ying-Yu Huang, Min Li
Hippocampal neurogenesis plays a critical role in the formation of new neurons during learning and memory development. Attenuation of neurogenesis in the brain is one of the primary causes of dementia in Alzheimer's disease (AD), and, conversely, modulating the process of hippocampal neurogenesis benefit patients with AD. Traditional Chinese medicine (TCM), particularly herbal medicine, has been in use for thousands of years in Asia and many regions of the world for the treatment of cancer, cardiovascular diseases and neurodegenerative diseases...
January 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28124605/increase-signaling-of-wnt-%C3%AE-catenin-pathway-and-presence-of-apoptosis-in-cerebellum-of-kindled-rats
#20
Carmen Rubio-Osornio, Artemio Rosiles-Abonce, Cristina Trejo-Solís, Moisés Rubio-Osornio, Cesar Mendoza, Verónica Custodio, Juan Carlos Martínez-Lazcano, Edith González, Carlos Paz
Epilepsy is one of the most common neurological disorders in humans, and the role of the cerebellum in its physiopathology remains the subject of study. The Purkinje cells (PC), whose axons target the dentate and interpositus nuclei, form the main cerebellar output to forebrain structures involved in epilepsy. Cerebellar atrophy related to loss of PC has been reported in chronic epilepsy although its mechanism remains unclear. Taking in account that an overexpression of β-Catenin has been related with cell death, here we present the signaling of β-Catenin and the type of PC death in cerebellum of rats with chronic seizures induced by the amygdaloid kindling model...
January 17, 2017: CNS & Neurological Disorders Drug Targets
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