scholarly journals Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3β signaling pathways

2012 ◽  
Vol 33 (7) ◽  
pp. 861-872 ◽  
Author(s):  
Ying Jin ◽  
Hai-juan Sui ◽  
Yan Dong ◽  
Qi Ding ◽  
Wen-hui Qu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Gsk 3Β

scholarly journals Integrin-linked kinase is a key signal factor involved in Nogo-66-induced inhibition of neurite outgrowth

2020 ◽  
Author(s):  
Ya-ping Yu ◽  
Qiang-ping Wang ◽  
Jian-Ying Shen ◽  
Nan-xiang Xiong ◽  
Hua Yu ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Signaling Pathway ◽  
Cortical Neurons ◽  
Glycogen Synthase ◽  
Growth Inhibitor ◽  
Neural Regeneration ◽  
Integrin Linked Kinase ◽  
Gsk 3Β

AbstractNogo-66, the extracellular domain of Nogo-A, has been identified as the most important myelin-associated neuronal growth inhibitor. Evidence suggested that Nogo-66 exert its neurite inhibition effect via a Nogo-66/Protein kinase B (PKB)/Glycogen synthase kinase-3β (GSK-3β)/tau signaling pathway. Integrin-linked kinase (ILK) is a serine/threonine kinase mediating axon upstream growth of PKB and GSK-3β. However, the contribution of ILK to the Nogo-66-induced inhibition of neurite, is not clear. In this study, we set out to reveal the role of ILK on Nogo-66 signaling in vitro and in vivo. To deteremine this directly, Recombinant adenoviruses were constructed to upregulate or downregulate the expresioon of ILK in Neuro 2a (N2a)and analysis the change of downstream molecule and neurite length. The results showed that Nogo-66 inhibited the phosphorylation of ILK, while ILK regulated the phosphorylation of PKB and GSK-3β, and the expression of tau in Nogo-66-treated N2a cells. ILK overexpression through lentivirus vector transfection reduced the inhibitory effect of neurite outgrowth induced by Nogo-66 in cortical neurons. The Tau expression in the complete spinal cord transection rat model was promoted by the overexpression of ILK. Our findings indicated that ILK is a key signal factor involved in Nogo-66-induced inhibition of neurite outgrowth. The mechanism of Nogo-66 signaling pathway was further explained and a proper target for the promotion of neural regeneration was also provided by this study.

scholarly journals Lin28 overexpression inhibits neurite outgrowth of primary cortical neurons in vitro

2018 ◽  
Vol 78 (4) ◽  
pp. 297-304
Author(s):  
Mohammad Iqbal Hossain Bhuiyan ◽  
Seong Yun Kim ◽  
Kyung-Ok Cho
Keyword(s):  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Primary Cortical Neurons

scholarly journals GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Meghan Morgan-Smith ◽  
Yaohong Wu ◽  
Xiaoqin Zhu ◽  
Julia Pringle ◽  
William D Snider
Keyword(s):  
Signaling Pathways ◽  
Cortical Neurons ◽  
Apical Dendrite ◽  
Regulatory Proteins ◽  
Radial Migration ◽  
Tangential Migration ◽  
Mouse Mutants ◽  
Basal Dendrites ◽  
Dendritic Arbors ◽  
Gsk 3Β

GSK-3 is an essential mediator of several signaling pathways that regulate cortical development. We therefore created conditional mouse mutants lacking both GSK-3α and GSK-3β in newly born cortical excitatory neurons. Gsk3-deleted neurons expressing upper layer markers exhibited striking migration failure in all areas of the cortex. Radial migration in hippocampus was similarly affected. In contrast, tangential migration was not grossly impaired after Gsk3 deletion in interneuron precursors. Gsk3-deleted neurons extended axons and developed dendritic arbors. However, the apical dendrite was frequently branched while basal dendrites exhibited abnormal orientation. GSK-3 regulation of migration in neurons was independent of Wnt/β-catenin signaling. Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased. Our data demonstrate that GSK-3 signaling is essential for radial migration and dendritic orientation and suggest that GSK-3 mediates these effects by phosphorylating key microtubule regulatory proteins.

Emodin induces neurite outgrowth through PI3K/Akt/GSK-3β-mediated signaling pathways in Neuro2a cells

2015 ◽  
Vol 588 ◽  
pp. 101-107 ◽  
Author(s):  
Shin-Ji Park ◽  
Mei Ling Jin ◽  
Hyun-Kyu An ◽  
Kyoung-Sook Kim ◽  
Min Jung Ko ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Neurite Outgrowth ◽  
Neuro2a Cells ◽  
Gsk 3Β

scholarly journals SCYL1BP1 modulates neurite outgrowth and regeneration by regulating the Mdm2/p53 pathway

2012 ◽  
Vol 23 (23) ◽  
pp. 4506-4514 ◽  
Author(s):  
Yonghua Liu ◽  
Ying Chen ◽  
Xiang Lu ◽  
Youhua Wang ◽  
Yinong Duan ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Axonal Regeneration ◽  
P53 Protein ◽  
Transcriptional Activator ◽  
Small Interfering Rnas ◽  
P53 Pathway ◽  
Neuronal Morphogenesis

SCY1-like 1–binding protein 1 (SCYL1BP1) is a newly identified transcriptional activator domain containing a protein with many unknown biological functions. Recently emerging evidence has revealed that it is a novel regulator of the p53 pathway, which is required for neurite outgrowth and regeneration. Here we present evidence that SCYL1BP1 inhibits nerve growth factor–mediated neurite outgrowth in PC12 cells and affects morphogenesis of primary cortical neurons by strongly decreasing the p53 protein level in vitro, all of which depends on SCYL1BP1's transcriptional activator domain. Exogenous p53 rescues neurite outgrowth and neuronal morphogenesis defects caused by SCYL1BP1. Furthermore, SCYL1BP1 can directly induce Mdm2 transcription, whereas inhibiting the function of Mdm2 by specific small interfering RNAs results in partial rescue of neurite outgrowth and neuronal morphogenesis defects induced by SCYL1BP1. In vivo experiments show that SCYL1BP1 can also depress axonal regeneration, whereas inhibiting the function of SCYL1BP1 by specific short hairpin RNA enhances it. Taken together, these data strongly suggested that SCYL1BP1 is a novel transcriptional activator in neurite outgrowth by directly modulating the Mdm2/p53-dependent pathway, which might play an important role in CNS development and axonal regeneration after injury.

scholarly journals Adiponectin as Well as Compressive Forces Regulate in vitro β-Catenin Expression on Cementoblasts via Mitogen-Activated Protein Kinase Signaling Activation

2021 ◽  
Vol 9 ◽  
Author(s):  
Jiawen Yong ◽  
Julia von Bremen ◽  
Gisela Ruiz-Heiland ◽  
Sabine Ruf
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Western Blots ◽  
Protein Levels ◽  
Mitogen Activated Protein ◽  
Gsk 3Β ◽  
Signaling Activation

We aimed to investigate the molecular effect that adiponectin exerts on cementoblasts especially in the presence of compressive forces. OCCM-30 cells (M. Somerman, NIH, NIDCR, United States) were used. Real-time reverse transcriptase–polymerase chain reaction (RT-PCR) and western blots were employed to verify if the mRNA and protein levels of adiponectin receptors (AdipoRs), mitogen-activated protein kinase (MAPK), and β-catenin signaling were influenced by compressive forces or adiponectin. Moreover, siRNAs targeting P38α, JNK1, ERK1, ERK2, and AdipoRs as well as pharmacological MAPK inhibition were performed. We found that compressive forces increase the expression of AdipoRs. Adiponectin and compression up-regulate P38α,JNK1, ERK1, and ERK2 as well as β-catenin gene expression. Western blots showed that co-stimuli activate the MAPK and β-catenin signaling pathways. MAPK inhibition alters the compression-induced β-catenin activation and the siRNAs targeting AdipoRs, P38α, and JNK1, showing the interaction of single MAPK molecules and β-catenin signaling in response to compression or adiponectin. Silencing by a dominantly negative version of P38α and JNK1 attenuates adiponectin-induced TCF/LEF reporter activation. Together, we found that light compressive forces activate β-catenin and MAPK signaling pathways. Adiponectin regulates β-catenin signaling principally by inactivating the GSK-3β kinase activity. β-Catenin expression was partially inhibited by MAPK blockade, indicating that MAPK plays a crucial role regulating β-catenin during cementogenesis. Moreover, adiponectin modulates GSK-3β and β-catenin mostly through AdipoR1. P38α is a key connector between β-catenin, TCF/LEF transcription, and MAPK signaling pathway.

scholarly journals RBM4 promotes neuronal differentiation and neurite outgrowth by modulating Numb isoform expression

2016 ◽  
Vol 27 (10) ◽  
pp. 1676-1683 ◽  
Author(s):  
Woan-Yuh Tarn ◽  
Hung-Che Kuo ◽  
Hsin-I. Yu ◽  
Shin-Wu Liu ◽  
Ching-Tzu Tseng ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Neurite Outgrowth ◽  
Cell Fate ◽  
Cortical Neurons ◽  
Neuronal Cell ◽  
Temporal Correlation ◽  
P19 Cells ◽  
Embryonic Mouse ◽  
Exon 9

RBM4 participates in cell differentiation by regulating tissue-specific alternative pre-mRNA splicing. RBM4 also has been implicated in neurogenesis in the mouse embryonic brain. Using mouse embryonal carcinoma P19 cells as a neural differentiation model, we observed a temporal correlation between RBM4 expression and a change in splicing isoforms of Numb, a cell-fate determination gene. Knockdown of RBM4 affected the inclusion/exclusion of exons 3 and 9 of Numb in P19 cells. RBM4-deficient embryonic mouse brain also exhibited aberrant splicing of Numb pre-mRNA. Using a splicing reporter minigene assay, we demonstrated that RBM4 promoted exon 3 inclusion and exon 9 exclusion. Moreover, we found that RBM4 depletion reduced the expression of the proneural gene Mash1, and such reduction was reversed by an RBM4-induced Numb isoform containing exon 3 but lacking exon 9. Accordingly, induction of ectopic RBM4 expression in neuronal progenitor cells increased Mash1 expression and promoted cell differentiation. Finally, we found that RBM4 was also essential for neurite outgrowth from cortical neurons in vitro. Neurite outgrowth defects of RBM4-depleted neurons were rescued by RBM4-induced exon 9–lacking Numb isoforms. Therefore our findings indicate that RBM4 modulates exon selection of Numb to generate isoforms that promote neuronal cell differentiation and neurite outgrowth.

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