scholarly journals Dpp and Hedgehog promote the glial response to neuronal apoptosis in the developing Drosophila visual system

PLoS Biology ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. e3001367
Author(s):  
Sergio B. Velarde ◽  
Alvaro Quevedo ◽  
Carlos Estella ◽  
Antonio Baonza
Keyword(s):  
Cell Death ◽  
Nervous System ◽  
Glial Cell ◽  
Glial Cells ◽  
Neuronal Apoptosis ◽  
Morphological Changes ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Jnk Pathway ◽  
Glial Cell Proliferation

Damage in the nervous system induces a stereotypical response that is mediated by glial cells. Here, we use the eye disc of Drosophila melanogaster as a model to explore the mechanisms involved in promoting glial cell response after neuronal cell death induction. We demonstrate that these cells rapidly respond to neuronal apoptosis by increasing in number and undergoing morphological changes, which will ultimately grant them phagocytic abilities. We found that this glial response is controlled by the activity of Decapentaplegic (Dpp) and Hedgehog (Hh) signalling pathways. These pathways are activated after cell death induction, and their functions are necessary to induce glial cell proliferation and migration to the eye discs. The latter of these 2 processes depend on the function of the c-Jun N-terminal kinase (JNK) pathway, which is activated by Dpp signalling. We also present evidence that a similar mechanism controls glial response upon apoptosis induction in the leg discs, suggesting that our results uncover a mechanism that might be involved in controlling glial cells response to neuronal cell death in different regions of the peripheral nervous system (PNS).

scholarly journals Down-Regulation of miR-23a-3p Mediates Irradiation-Induced Neuronal Apoptosis

2020 ◽  
Vol 21 (10) ◽  
pp. 3695 ◽  
Author(s):  
Boris Sabirzhanov ◽  
Oleg Makarevich ◽  
James Barrett ◽  
Isabel L. Jackson ◽  
Alan I. Faden ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Cytochrome C ◽  
Neuronal Apoptosis ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Negative Regulator ◽  
Down Regulation ◽  
Bcl2 Family ◽  
Mitochondrial Outer Membrane Permeabilization

Radiation-induced central nervous system toxicity is a significant risk factor for patients receiving cancer radiotherapy. Surprisingly, the mechanisms responsible for the DNA damage-triggered neuronal cell death following irradiation have yet to be deciphered. Using primary cortical neuronal cultures in vitro, we demonstrated that X-ray exposure induces the mitochondrial pathway of intrinsic apoptosis and that miR-23a-3p plays a significant role in the regulation of this process. Primary cortical neurons exposed to irradiation show the activation of DNA-damage response pathways, including the sequential phosphorylation of ATM kinase, histone H2AX, and p53. This is followed by the p53-dependent up-regulation of the pro-apoptotic Bcl2 family molecules, including the BH3-only molecules PUMA, Noxa, and Bim, leading to mitochondrial outer membrane permeabilization (MOMP) and the release of cytochrome c, which activates caspase-dependent apoptosis. miR-23a-3p, a negative regulator of specific pro-apoptotic Bcl-2 family molecules, is rapidly decreased after neuronal irradiation. By increasing the degradation of PUMA and Noxa mRNAs in the RNA-induced silencing complex (RISC), the administration of the miR-23a-3p mimic inhibits the irradiation-induced up-regulation of Noxa and Puma. These changes result in an attenuation of apoptotic processes such as MOMP, the release of cytochrome c and caspases activation, and a reduction in neuronal cell death. The neuroprotective effects of miR-23a-3p administration may not only involve the direct inhibition of pro-apoptotic Bcl-2 molecules downstream of p53 but also include the attenuation of secondary DNA damage upstream of p53. Importantly, we demonstrated that brain irradiation in vivo results in the down-regulation of miR-23a-3p and the elevation of pro-apoptotic Bcl2-family molecules PUMA, Noxa, and Bax, not only broadly in the cortex and hippocampus, except for Bax, which was up-regulated only in the hippocampus but also selectively in isolated neuronal populations from the irradiated brain. Overall, our data suggest that miR-23a-3p down-regulation contributes to irradiation-induced intrinsic pathways of neuronal apoptosis. These regulated pathways of neurodegeneration may be the target of effective neuroprotective strategies using miR-23a-3p mimics to block their development and increase neuronal survival after irradiation.

scholarly journals Neuronal cell life, death, and axonal degeneration as regulated by the BCL-2 family proteins

2020 ◽  
Vol 28 (1) ◽  
pp. 108-122
Author(s):  
James M. Pemberton ◽  
Justin P. Pogmore ◽  
David W. Andrews
Keyword(s):  
Cell Death ◽  
Neuronal Apoptosis ◽  
Axonal Degeneration ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Axon Degeneration ◽  
Mitochondrial Outer Membrane ◽  
Future Research ◽  
System Disease ◽  
Family Protein

AbstractAxonal degeneration and neuronal cell death are fundamental processes in development and contribute to the pathology of neurological disease in adults. Both processes are regulated by BCL-2 family proteins which orchestrate the permeabilization of the mitochondrial outer membrane (MOM). MOM permeabilization (MOMP) results in the activation of pro-apoptotic molecules that commit neurons to either die or degenerate. With the success of small-molecule inhibitors targeting anti-apoptotic BCL-2 proteins for the treatment of lymphoma, we can now envision the use of inhibitors of apoptosis with exquisite selectivity for BCL-2 family protein regulation of neuronal apoptosis in the treatment of nervous system disease. Critical to this development is deciphering which subset of proteins is required for neuronal apoptosis and axon degeneration, and how these two different outcomes are separately regulated. Moreover, noncanonical BCL-2 family protein functions unrelated to the regulation of MOMP, including impacting necroptosis and other modes of cell death may reveal additional potential targets and/or confounders. This review highlights our current understanding of BCL-2 family mediated neuronal cell death and axon degeneration, while identifying future research questions to be resolved to enable regulating neuronal survival pharmacologically.

Symposium 4: Neuronal Cell Death in the Nervous System

1994 ◽  
Vol 4 (4) ◽  
pp. 301-302 ◽  
Author(s):  
Donald L. Price
Keyword(s):  
Cell Death ◽  
Nervous System ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals Isoflavones Induce BEX2-Dependent Autophagy to Prevent ATR-Induced Neurotoxicity in SH-SY5Y Cells

2017 ◽  
Vol 43 (5) ◽  
pp. 1866-1879 ◽  
Author(s):  
Peng Li ◽  
Kun Ma ◽  
Hao-Yu Wu ◽  
Yan-Ping Wu ◽  
Bai-Xiang Li
Keyword(s):  
Cell Death ◽  
Neuronal Apoptosis ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Green Tea Polyphenols ◽  
Key Factors ◽  
Related Proteins ◽  
Catabolic Process ◽  
Plant Compounds

Background/Aims: Atrazine (ATR) is a broad-spectrum herbicide in wide use around the world. However, ATR is neurotoxic and can cause cell death in dopaminergic neurons, leading to neurodegenerative disorders. Autophagy is the basic cellular catabolic process involving the degradation of proteins and damaged organelles. Studies have shown that certain plant compounds can induce autophagy and prevent neuronal cell death. This prompted us to investigate plant compounds that might reduce the neurotoxic effects of ATR. Methods: By CCK-8 and flow cytometry, we tested the ability of five candidate compounds—isoflavones, resveratrol, quercetin, curcumin, and green tea polyphenols—to protect cells from ATR. Changes in the expression of tyrosine hydroxylase (TH) and brain-expressed X-linked 2 (BEX2), autophagy-related proteins and key factors in mTOR signaling, were detected by Western blotting. Results: Isoflavones had the strongest activity against ATR-induced neuronal apoptosis. ATR reduced the expression of TH and BEX2, whereas isoflavones increased TH and BEX2 expression. In addition, ATR inhibited autophagy, whereas isoflavones induced autophagy through the accumulation of LC3-II and decreased expression of p62; this effect was abolished by 3-methyladenine (3-MA). Furthermore, BEX2 siRNA abolished isoflavone-mediated autophagy and neuroprotection in vitro. Conclusion: Isoflavones activate BEX2-dependent autophagy, protecting against ATR-induced neuronal apoptosis.

scholarly journals dl-3-n-Butylphthalide prevents neuronal cell death after focal cerebral ischemia in mice via the JNK pathway

2010 ◽  
Vol 1359 ◽  
pp. 216-226 ◽  
Author(s):  
Jimei Li ◽  
Yin Li ◽  
Molly Ogle ◽  
Xin Zhou ◽  
Minke Song ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Jnk Pathway

scholarly journals Neurovascular Impairment and Therapeutic Strategies in Diabetic Retinopathy

2021 ◽  
Vol 19 (1) ◽  
pp. 439
Author(s):  
Toshiyuki Oshitari
Keyword(s):  
Cell Death ◽  
Diabetic Retinopathy ◽  
Glial Cells ◽  
Vision Loss ◽  
Current Knowledge ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Therapeutic Strategies ◽  
Irreversible Change ◽  
Interdependent Relationships

Diabetic retinopathy has recently been defined as a highly specific neurovascular complication of diabetes. The chronic progression of the impairment of the interdependence of neurovascular units (NVUs) is associated with the pathogenesis of diabetic retinopathy. The NVUs consist of neurons, glial cells, and vascular cells, and the interdependent relationships between these cells are disturbed under diabetic conditions. Clinicians should understand and update the current knowledge of the neurovascular impairments in diabetic retinopathy. Above all, neuronal cell death is an irreversible change, and it is directly related to vision loss in patients with diabetic retinopathy. Thus, neuroprotective and vasoprotective therapies for diabetic retinopathy must be established. Understanding the physiological and pathological interdependence of the NVUs is helpful in establishing neuroprotective and vasoprotective therapies for diabetic retinopathy. This review focuses on the pathogenesis of the neurovascular impairments and introduces possible neurovascular protective therapies for diabetic retinopathy.

scholarly journals Oncogenic BRAF V600E induces glial proliferation through ERK and neuronal death through JNK

2021 ◽  
Author(s):  
Qing Ye ◽  
Nasser Al-Kuwari ◽  
Pranay Srivast ◽  
Xiqun Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Glial Cells ◽  
Primary Cultures ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Braf V600e ◽  
Downstream Effectors ◽  
Mutational Activation

Abstract Background Activating V600E in BRAF is a common driver mutation in cancers of multiple tissue origins, including melanoma and glioma. BRAFV600E has also been implicated in neurodegeneration. The present study aims to characterize BRAFV600E on cell death and survival in three major cell types of the CNS: neurons, astrocytes, and microglia. Methods Multiple primary cultures and cell lines of glial cells and neurons were employed. BRAFV600E as well as BRAFWT expression was mediated by lentivirus or retrovirus. Blockage of downstream effectors were achieved by siRNA. Gene expression data from patients with Parkinson’s disease was analyzed. Results In astrocytes and microglia, BRAFV600E induces cell proliferation, and the proliferative effect in microglia is mediated by activated ERK but not JNK. Conditioned medium from BRAFV600E-expressing microglia induced neuronal cell death. In neuronal cells, BRAFV600E directly induces cell death, through JNK but not ERK. We further show that BRAF-related genes are enriched in pathways in patients with Parkinson’s disease. Conclusions Our study identifies distinct consequences mediated by distinct downstream effectors in dividing glial cells and in neurons following the same BRAF mutational activation and a causal link between BRAF-activated microglia and neuronal cell death that does not require physical proximity. It provides insight into a possibly important role of BRAF in neurodegeneration as a result of either dysregulated BRAF in neurons or its impact on glial cells.

scholarly journals Na+, K+-ATPase inhibition induces neuronal cell death in rat hippocampal slice cultures: Association with GLAST and glial cell abnormalities

2018 ◽  
Vol 138 (3) ◽  
pp. 167-175 ◽  
Author(s):  
Yuki Kurauchi ◽  
Kazuki Noma ◽  
Akinori Hisatsune ◽  
Takahiro Seki ◽  
Hiroshi Katsuki
Keyword(s):  
Cell Death ◽  
Glial Cell ◽  
Hippocampal Slice ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Hippocampal Slice Cultures ◽  
Atpase Inhibition
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