Peroxynitrite enhances self-renewal, proliferation and neuronal differentiation of neural stem/progenitor cells through activating HIF-1α and Wnt/β-catenin signaling pathway

Chen, Xingmiao; Zhou, Binghua; Yan, Tingting; Wu, Hao; Feng, Jie; Chen, Hansen; Gao, Chong; Tao, Ping; Yang, Dan; Shen, Jiangang

doi:10.1016/j.freeradbiomed.2018.02.011

Cited by 34 publications

(27 citation statements)

References 52 publications

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“…Corroborating our earlier findings, a number of recent studies have highlighted the critical importance of WβC crosstalk with survival and inflammatory pathways in inciting neurogenesis and neurorepair (Chen et al, ; Kalamakis et al, ; Kase, Otsu, Shimazaki, & Okano, ; Mishra et al, ; Morrow & Moore, ; Ray et al, ; Singh, Mishra, Bharti, et al, ; Singh, Mishra, Mohanbhai, et al, ; Singh, Mishra, & Shukla, ).…”

Section: Introductionsupporting

confidence: 78%

“…Herein, after a description of the key Wnt‐signalling components and a synopsis of adult neurogenesis in PD, we will focus on the role of WβC‐signalling as a common final pathway in mediating NSC regulation, from development to aging and PD degeneration. We aim to survey recent literature in the field supporting the upregulation of WβC as a means to re‐activate neurogenesis and incite regeneration in the injured brain, particularly in the context of modalities through which the inherent self‐repair capacities of the aged PD brain, can be engaged (Chen et al, ; Kase et al, ; Kaur, Saunders, & Tolwinski, ; Mishra et al, ; Zeng et al, ; Zhao, et al, ; Zhang et al, a,b,c; and following sections).…”

Section: Introductionmentioning

confidence: 99%

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Parkinson's disease, aging and adult neurogenesis: Wnt/β‐catenin signalling as the key to unlock the mystery of endogenous brain repair

et al. 2020

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A common hallmark of age‐dependent neurodegenerative diseases is an impairment of adult neurogenesis. Wingless‐type mouse mammary tumor virus integration site (Wnt)/β‐catenin (WβC) signalling is a vital pathway for dopaminergic (DAergic) neurogenesis and an essential signalling system during embryonic development and aging, the most critical risk factor for Parkinson's disease (PD). To date, there is no known cause or cure for PD. Here we focus on the potential to reawaken the impaired neurogenic niches to rejuvenate and repair the aged PD brain. Specifically, we highlight WβC‐signalling in the plasticity of the subventricular zone (SVZ), the largest germinal region in the mature brain innervated by nigrostriatal DAergic terminals, and the mesencephalic aqueduct‐periventricular region (Aq‐PVR) Wnt‐sensitive niche, which is in proximity to the SNpc and harbors neural stem progenitor cells (NSCs) with DAergic potential. The hallmark of the WβC pathway is the cytosolic accumulation of β‐catenin, which enters the nucleus and associates with T cell factor/lymphoid enhancer binding factor (TCF/LEF) transcription factors, leading to the transcription of Wnt target genes. Here, we underscore the dynamic interplay between DAergic innervation and astroglial‐derived factors regulating WβC‐dependent transcription of key genes orchestrating NSC proliferation, survival, migration and differentiation. Aging, inflammation and oxidative stress synergize with neurotoxin exposure in “turning off” the WβC neurogenic switch via down‐regulation of the nuclear factor erythroid‐2‐related factor 2/Wnt‐regulated signalosome, a key player in the maintenance of antioxidant self‐defense mechanisms and NSC homeostasis. Harnessing WβC‐signalling in the aged PD brain can thus restore neurogenesis, rejuvenate the microenvironment, and promote neurorescue and regeneration.

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Section: Introductionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Parkinson's disease, aging and adult neurogenesis: Wnt/β‐catenin signalling as the key to unlock the mystery of endogenous brain repair

et al. 2020

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“…The Wnt pathway is closely associated with cerebral cortex development, and Wnt pathway activation via β-catenin dephosphorylation causes the massive expansion of the cerebral cortex (Chenn 2008). In response to cerebral ischemiareperfusion injury, Wnt pathway activation is positively correlated with hypoxia-inducible factor-1 (HIF-1) and promotes neural stem cell proliferation and self-renewal in vivo (Chen et al 2018). Moreover, Wnt pathway activation could increase neuroprotective autophagic flux in ischemia-mediated neuroinjury (Shi et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Sirt3 inhibits cerebral ischemia-reperfusion injury through normalizing Wnt/β-catenin pathway and blocking mitochondrial fission

Zhao

Luo

Chen

et al. 2018

Cell Stress and Chaperones

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Cerebral ischemia-reperfusion injury (IRI) potentiates existing brain damage and increases mortality and morbidity via poorly understood mechanisms. The aim of our study is to investigate the role of Sirtuin 3 (Sirt3) in the development and progression of cerebral ischemia-reperfusion injury with a focus on mitochondrial fission and the Wnt/β-catenin pathway. Our data indicated that Sirt3 was downregulated in response to cerebral IRI. However, the overexpression of Sirt3 reduced the brain infarction area and repressed IRI-mediated neuron apoptosis. Functional assays demonstrated that IRI augmented mitochondrial fission, which induced ROS overproduction, redox imbalance, mitochondrial pro-apoptotic protein leakage, and caspase-9-dependent cell death pathway activation. However, the overexpression of Sirt3 blocked mitochondrial fission and induced pro-survival signals in neurons subjected to IRI. At the molecular level, our data further illustrated that the Wnt/β-catenin pathway is required for the neuroprotection exerted by Sirt3 overexpression. Wnt/β-catenin pathway activation via inhibiting β-catenin phosphorylation attenuates mitochondrial fission and mitochondrial apoptosis. Collectively, our data show that cerebral IRI is associated with Sirt3 downregulation, Wnt/β-catenin pathway phosphorylated inactivation, and mitochondrial fission initiation, causing neurons to undergo caspase-9-dependent cell death. Based on this, strategies for enhancing Sirt3 activity and activating the Wnt/β-catenin pathway could be therapeutic targets for treating cerebral ischemia-reperfusion injury.

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“…A further insight into this mechanism was provided by Chen and colleagues, who reported that after ischemia-reperfusion injury in rats, peroxynitrite was produced, activating the proliferation and differentiation of NSCs via the upregulation of HIF1α and Wnt signaling. However, higher doses of peroxynitrite were neurotoxic [160]. Another intrinsic factor that might play a role in the reaction of nervous tissue to ischemic injury is microRNA (miRNA)-148b, since its over-expression has been reported in the SVZ of the ischemic rat brain.…”

Section: The Impact Of Wnt Signaling On Different Cell Types During Imentioning

confidence: 99%

Glia and Neural Stem and Progenitor Cells of the Healthy and Ischemic Brain: The Workplace for the Wnt Signaling Pathway

Knotek

Janečková

Kriška

et al. 2020

Genes

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Wnt signaling plays an important role in the self-renewal, fate-commitment and survival of the neural stem/progenitor cells (NS/PCs) of the adult central nervous system (CNS). Ischemic stroke impairs the proper functioning of the CNS and, therefore, active Wnt signaling may prevent, ameliorate, or even reverse the negative effects of ischemic brain injury. In this review, we provide the current knowledge of Wnt signaling in the adult CNS, its status in diverse cell types, and the Wnt pathway’s impact on the properties of NS/PCs and glial cells in the context of ischemic injury. Finally, we summarize promising strategies that might be considered for stroke therapy, and we outline possible future directions of the field.

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Peroxynitrite enhances self-renewal, proliferation and neuronal differentiation of neural stem/progenitor cells through activating HIF-1α and Wnt/β-catenin signaling pathway

Cited by 34 publications

References 52 publications

Parkinson's disease, aging and adult neurogenesis: Wnt/β‐catenin signalling as the key to unlock the mystery of endogenous brain repair

Parkinson's disease, aging and adult neurogenesis: Wnt/β‐catenin signalling as the key to unlock the mystery of endogenous brain repair

Sirt3 inhibits cerebral ischemia-reperfusion injury through normalizing Wnt/β-catenin pathway and blocking mitochondrial fission

Glia and Neural Stem and Progenitor Cells of the Healthy and Ischemic Brain: The Workplace for the Wnt Signaling Pathway

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