Redox-regulated fate of neural stem progenitor cells

Prozorovski, Timour; Schneider, Reiner; Berndt, Carsten; Hartung, Hans‐Peter; Aktaş, Orhan

doi:10.1016/j.bbagen.2015.01.022

Cited by 40 publications

(30 citation statements)

References 208 publications

(279 reference statements)

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“…NPCs can be quiescent but will undergo activation with spiking ROS levels and proliferate to give rise to more NPCs. Similarly, differentiating cells have more ROS than its ancestor progenitors due to metabolic shift from aerobic glycolysis to oxidative phosphorylation [ 50 , 51 ]. An in vitro report showed that post mitotic exit of neuroblasts to form immature neurons was associated with increased ROS levels and enhanced levels of mitochondrial electron transport proteins [ 52 ].…”

Section: Ros As a Mediator In Growth Factor Response And Cell Prolmentioning

confidence: 99%

“…ROS also are involved in NPC differentiation as was recently reviewed [ 51 ]. Overall, NPCs' proliferation has been inversely related to oxygen levels, and therefore in hypoxic zones, NPCs remain mostly proliferative.…”

Section: Ros and Npc Proliferationmentioning

confidence: 99%

“…Overall, NPCs' proliferation has been inversely related to oxygen levels, and therefore in hypoxic zones, NPCs remain mostly proliferative. Upon the induction of mitochondrial activity and oxidative phosphorylation, the rise in ROS levels or exposure to stressful conditions inhibits proliferation and promotes cell differentiation [ 51 ]. Understanding ROS production and regulation in NPCs provide a window of opportunity to optimize cell proliferation and differentiation.…”

Section: Ros and Npc Proliferationmentioning

confidence: 99%

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Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate

Iqbal

Eftekharpour

2017

Stem Cells International

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In 1990s, reports of discovery of a small group of cells capable of proliferation and contribution to formation of new neurons in the central nervous system (CNS) reversed a century-old concept on lack of neurogenesis in the adult mammalian brain. These cells are found in all stages of human life and contribute to normal cellular turnover of the CNS. Therefore, the identity of regulating factors that affect their proliferation and differentiation is a highly noteworthy issue for basic scientists and their clinician counterparts for therapeutic purposes. The cues for such control are embedded in developmental and environmental signaling through a highly regulated tempo-spatial expression of specific transcription factors. Novel findings indicate the importance of reactive oxygen species (ROS) in the regulation of this signaling system. The elusive nature of ROS signaling in many vital processes from cell proliferation to cell death creates a complex literature in this field. Here, we discuss the emerging thoughts on the importance of redox regulation of proliferation and maintenance in mammalian neural stem and progenitor cells under physiological and pathological conditions. The current knowledge on ROS-mediated changes in redox-sensitive proteins that govern the molecular mechanisms in proliferation and differentiation of these cells is reviewed.

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Section: Ros As a Mediator In Growth Factor Response And Cell Prolmentioning

confidence: 99%

Section: Ros and Npc Proliferationmentioning

confidence: 99%

Section: Ros and Npc Proliferationmentioning

confidence: 99%

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Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate

Iqbal

Eftekharpour

2017

Stem Cells International

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“…Furthermore, variations in ROS levels can have a profound effect on stem cell fate and survival [25], which prompted us to investigate the role of stress-sensing JNK in regulating mitochondrial ROS levels in NSPs. Mitochondrial ROS levels were evaluated using the median fluorescence intensity of NSPs incubated with Mito-SOX TM Red reagent, which specifically detects O • 2 -in the mitochondria of live cells.…”

Section: Inhibition Of Jnk Kinase Increases Levels Of Mitochondrial Smentioning

confidence: 99%

“…Elucidation of the biochemical events involved in maintaining the redox homeostasis in neural stem cells is a promising area of investigation toward gaining a greater understanding of age-related disorders of the CNS, as well as the neural circuits that control metabolic pathways, including food intake and energy expenditure [24,25]. Furthermore, variations in ROS levels can have a profound effect on stem cell fate and survival [25], which prompted us to investigate the role of stress-sensing JNK in regulating mitochondrial ROS levels in NSPs.…”

Section: Inhibition Of Jnk Kinase Increases Levels Of Mitochondrial Smentioning

confidence: 99%

<b><i>c-Jun N-Terminal Kinase</i></b> Inhibition Induces Mitochondrial Oxidative Stress and Decreases Survival in Human Neural Stem Progenitors

et al. 2018

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Neural stem cells are attracting enormous attention in regenerative medicine due to their ability to self-renew and differentiate into the cell lineages that constitute the central nervous system. However, little is known about the mechanism underlying the regulation of their redox environment, which is essential for homeostatic cellular functions. The redox-modulated c-Jun N-terminal kinases (JNK) are a molecular switch in stress signal transduction and are involved in numerous brain functions. Using a selective but broad-spectrum inhibitor of JNK 1/2/3, we investigated the role of JNK in regulating the levels of reactive oxygen species in mitochondria, mitochondrial membrane potential, viability, proliferation and lineage alterations in human H9-derived neural stem/progenitor cells (NSPs). Relative to diluent control, incubation of the NSPs for 24 h with SP600125, an anthrapyrazolone inhibitor of JNK, resulted in increased abundance of mitochondrial superoxide radicals (p < 0.05), concomitant with decreases in mitochondrial membrane potential (p < 0.001), while maintaining a consistent and stable mitochondrial mass. Whereas H9-derived NSPs collectively express Nestin, a marker for neural stem cells, a panel of cell surface markers analyzed by flow cytometry revealed that they are a heterogeneous population that sustains this diversity after JNK inhibition. In addition, the levels of nuclear forkhead homeobox type O3a (FoxO3a), a regulator of redox homeostasis, decreased, which was associated with a decrease in overall cell viability as measured by Annexin V staining (p < 0.001), and supported by an increased level of cleaved Poly-ADP-ribose polymerase and decreased survivin expression. However, staining with the proliferation marker, Ki67, revealed the presence of a significant percentage of proliferating cells in the treated population. Together, the results support a role for JNK in the redox-homeostasis and fate of NSPs. Identifying regulators of the cellular redox environment will enhance our understanding of the mechanisms that modulate neural stem cell functions and optimize therapeutic applications targeting JNK.

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Mitochondria in Neurogenesis: Implications for Mitochondrial Diseases

Brunetti

Dykstra

et al. 2021

Stem Cells

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Mitochondria are organelles with recognized key roles in cellular homeostasis, including bioenergetics, redox, calcium signaling, and cell death. Mitochondria are essential for neuronal function, given the high energy demands of the human brain. Consequently, mitochondrial diseases affecting oxidative phosphorylation (OXPHOS) commonly exhibit neurological impairment. Emerging evidence suggests that mitochondria are important not only for mature postmitotic neurons but also for the regulation of neural progenitor cells (NPCs) during the process of neurogenesis. These recent findings put mitochondria as central regulator of cell fate decisions during brain development. OXPHOS mutations may disrupt the function of NPCs and thereby impair the metabolic programming required for neural fate commitment. Promoting the mitochondrial function of NPCs could therefore represent a novel interventional approach against incurable mitochondrial diseases.

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Redox-regulated fate of neural stem progenitor cells

Cited by 40 publications

References 208 publications

Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate

Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate

<b><i>c-Jun N-Terminal Kinase</i></b> Inhibition Induces Mitochondrial Oxidative Stress and Decreases Survival in Human Neural Stem Progenitors

Mitochondria in Neurogenesis: Implications for Mitochondrial Diseases

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