Neuroglobin expression in neurogenesis

Haines, Bryan; Xie, Lin; Spusta, Steve; Zeng, Xianmin; Jin, Kunlin; Greenberg, David A.

doi:10.1016/j.neulet.2013.04.039

Cited by 22 publications

(13 citation statements)

References 37 publications

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“…SIM1 is involved in food intake and energy expenditure in accordance with a possible role of NGB in maintaining energy homeostasis in neurons. In the neurogenic subventricular zone in adult rat brain SOX‐3 and SOX‐4, which are involved in the maintenance of progenitor neuronal cells, are coexpressed with NGB, coherent with a role of NGB in neurogenesis, migration and differentiation .…”

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confidence: 75%

Genomic lens on neuroglobin transcription

et al. 2014

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Neuroglobin is a brain globin with neuroprotective effects against ischemia and related pathological processes, acting as O 2 sensor and antiapoptotic pathway transducer. Here, we survey data on neuroanatomical coexpression of transcription factors, epigenetic signature and predictive transcription factor binding sites at the neuroglobin gene locus to find hints of pathways to neuroglobin transcriptional regulation. These data provide a glimpse of how neuroglobin expression may translate into neuronal diversity and function, as well as disease. Keywords: neuroglobin; transcriptional regulation; genomics Neuroglobin (NGB) is the first vertebrate nerve globin identified in the nervous tissues of mice and humans (1). It is induced by hypoxia and oxidative stress and leads to neuroprotection, but the molecular mechanisms of induction and protection are poorly understood. NGB overexpression is protective in animal models of several diseases such as stroke, Alzheimer's disease, tumor progression and glaucoma (2-4). There are two main hypotheses on the potential mechanisms of neuroprotection by NGB: reactive oxigen species (ROS)-scavenging in mitochondria metabolism and interference with apoptosis signaling. NGB binds several ligands, including O 2 , CO and NO; the ligand-linked conformational changes provide a surface for formation of protein complexes that may account for the involvement of NGB in a protective signaling mechanism. NGB interacts with Rho GTPase family members and in association with cytochrome c, it prevents its release in the cytosol resulting in neuroprotection against death induced by injuring stimuli (5). Therefore, understanding how NGB is regulated and which factors orchestrate its transcriptional activation is pivotal to underpinning its cell function and developing pharmacological approaches to its control.Systems biology approaches, integrating gene expression profiling and anatomical maps with genomic data of transcription factor binding sites (TFBSs) and chromatin epigenetic modifications, provide correlative networks extremely powerful to support hypothesis driven studies on specific proteins in the brain (6). To apply this concept to NGB regulation, in the first part of this article we go through available data on NGB expression in specific brain regions and its coexpression with TFs. Next, we analyze epigenetic marks and predicted consensus TF binding motifs at the NGB genomic locus.We used the Allen Human Brain Atlas (AHBA) (http:// www.brain-map.org), a comprehensive map of transcripts with anatomically complete coverage of the entire adult brain (7,8). NGB expression is observed in focal regions of the brain (9), and the pattern is similar in rat and human brain, as reported in Fig. 1A. NGB is highly expressed in the hypothalamus, in particular in the anterior hypothalamic area and in the lateral hypothalamic area (mammillary region), in the paraventricular nucleus and in the arcuate nucleus, in the dorsomedial hypothalamic nucleus and in the preoptic area. In addition, NGB is...

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confidence: 75%

Genomic lens on neuroglobin transcription

et al. 2014

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“…Interestingly, a number of studies imply a potential role of Ngb in neurogenesis. Ngb has been reported to be expressed early in the course of neuronal differentiation 26 . Moreover, mitochondria play a key role in neurogenesis by providing ATP as the energy for cytoskeleton remodeling and neurite outgrowth 27 .…”

Section: Introductionmentioning

confidence: 99%

Neuroglobin promotes neurogenesis through Wnt signaling pathway

Cheng

Liu

et al. 2018

Cell Death Dis

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Neuroglobin (Ngb) has been demonstrated by our lab and others to be neuroprotective against neurological disorders including stroke. However, the roles of Ngb in neurogenesis remain elusive. Neurogenesis can occur in adulthood and can be induced by pathological conditions in the brain such as stroke, and significantly contributes to functional recovery, thus enhancing endogenous neurogenesis may be a promising therapeutic strategy for neurodegenerative diseases. In this study we aimed to investigate the roles of Ngb in neurogenesis using Lentivirus overexpressing Ngb (Lv-Ngb). We show that Ngb overexpression promoted the proliferation of neural progenitor cells (NPC) marked by increased neurosphere number and size. Ngb overexpression also enhanced neuronal differentiation of cultured NPC under differentiation conditions. Moreover, subventricular injection of Lv-Ngb in mice after middle cerebral artery occlusion (MCAO) increased PSA-NCAM positive neuroblasts and Tuj1 positive immature neurons, suggesting that Ngb overexpression promotes neurogenesis in mice brain after stroke. We further show that the pro-neurogenesis effect of Ngb overexpression might be mediated through Dvl1 up-regulation, and subsequent activation of Wnt signaling, indicated by increased nuclear localization of beta-catenin. These results suggest that Ngb may play an important role in promoting neurogenesis in neurodegenerative diseases such as stroke, which may eventually benefit the development of stroke therapeutics targeting neurogenesis through Ngb upregulation.

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“…As an essential effector of canonical Wnt/β-Catenin signaling pathway, Dvl1 is an important regulator in the proliferation and differentiation of neural progenitor cells [ 34 ]. Emerging data suggested that Ngb plays a key role in neurodevelopment and neurogenesis [ 35 ], and a most recent study showed that the loss of Ngb resulted in enhanced cell cycle progression and increased proliferation of neural stem cells [ 36 ]. However, the underlying molecular mechanisms still remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Neuroglobin Regulates Wnt/β-Catenin and NFκB Signaling Pathway through Dvl1

Xun

Tang

et al. 2018

IJMS

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Neuroglobin is an endogenous neuroprotective protein, but the underlying neuroprotective mechanisms remain to be elucidated. Our previous yeast two-hybrid screening study identified that Dishevelled-1, a key hub protein of Wnt/β-Catenin signaling, is an interaction partner of Neuroglobin. In this study, we further examined the role of Neuroglobin in regulating Dishevelled-1 and the downstream Wnt/β-Catenin and NFκB signaling pathway. We found that Neuroglobin directly interacts with Dishevelled-1 by co-immunoprecipitation, and the two proteins are co-localized in both cytoplasma and nucleus of SK-N-SH cells. Moreover, the ectopic expression of Neuroglobin promotes the degradation of exogenous and endogenous Dishevelled-1 through the proteasomal degradation pathway. Furthermore, our results showed that Neuroglobin significantly inhibits the luciferase activity of Topflash reporter and the expression of β-Catenin mediated by Dishevelled-1 in SK-N-SH cells. In addition, we also documented that Neuroglobin enhances TNF-α-induced NFκB activation via down-regulating Dishevelled-1. Finally, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assays showed that Neuroglobin is an important neuroprotectant that protects SK-N-SH cells from TNF-α-induced decrease in cell viability. Taken together, these findings demonstrated that Neuroglobin functions as an important modulator of the Wnt/β-Catenin and NFκB signaling pathway through regulating Dishevelled-1.

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Neuroglobin expression in neurogenesis

Cited by 22 publications

References 37 publications

Genomic lens on neuroglobin transcription

Genomic lens on neuroglobin transcription

Neuroglobin promotes neurogenesis through Wnt signaling pathway

Neuroglobin Regulates Wnt/β-Catenin and NFκB Signaling Pathway through Dvl1

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