Multiple signaling events in amyloid β-induced, oxidative stress-dependent neuronal apoptosis

2003 ◽  
Vol 35 (1) ◽  
pp. 45-58 ◽  
Author(s):  
E Tamagno
Keyword(s):  
Oxidative Stress ◽  
Neuronal Apoptosis ◽  
Amyloid Β ◽  
Signaling Events ◽  
Stress Dependent ◽  
Multiple Signaling

scholarly journals Oxidative stress–dependent phosphorylation activates ZNRF1 to induce neuronal/axonal degeneration

2015 ◽  
Vol 211 (4) ◽  
pp. 881-896 ◽  
Author(s):  
Shuji Wakatsuki ◽  
Akiko Furuno ◽  
Makiko Ohshima ◽  
Toshiyuki Araki
Keyword(s):  
Oxidative Stress ◽  
Ubiquitin Ligase ◽  
Wallerian Degeneration ◽  
Neuronal Apoptosis ◽  
Axonal Degeneration ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Growth Factor Receptor ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Ligase Activity ◽  
Stress Dependent

Oxidative stress is a well-known inducer of neuronal apoptosis and axonal degeneration. We previously showed that the E3 ubiquitin ligase ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B activation. We now demonstrate that oxidative stress serves as an activator of the ubiquitin ligase activity of ZNRF1 by inducing epidermal growth factor receptor (EGFR)–mediated phosphorylation at the 103rd tyrosine residue and that the up-regulation of ZNRF1 activity by oxidative stress leads to neuronal apoptosis and Wallerian degeneration. We also show that nicotinamide adenine dinucleotide phosphate–reduced oxidase activity is required for the EGFR-dependent phosphorylation-induced activation of ZNRF1 and resultant AKT degradation via the ubiquitin proteasome system to induce Wallerian degeneration. These results indicate the pathophysiological significance of the EGFR–ZNRF1 pathway induced by oxidative stress in the regulation of neuronal apoptosis and Wallerian degeneration. A deeper understanding of the regulatory mechanism for ZNRF1 catalytic activity via phosphorylation will provide a potential therapeutic avenue for neurodegeneration.

Berberine nanoencapsulation attenuates hallmarks of scoplomine induced Alzheimer's-like disease in rats

2020 ◽  
Vol 15 ◽  
Author(s):  
Samar R. Saleh ◽  
Mariam M. Abady ◽  
Mohammed Nofal ◽  
Nashwa W. Yassa ◽  
Mohamed S. Abdel-latif ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Histopathological Examination ◽  
Memory Function ◽  
Amyloid Β ◽  
Active Pharmaceutical Ingredient ◽  
Isoquinoline Alkaloid ◽  
Drug Uptake ◽  
Male Rats ◽  
Morris Water Maze Test ◽  
Neuroprotective Effects

Background: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, antiinflammatory, cholesterol-lowering effect, and inhibition of Aβ production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments. Methods: BBR-NPs were formulated using ionic gelation method and tripolyphosphate was chosen as a cross linker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty six Wistar male rats were randomly distributed into: three control groups, received saline, polyethylene glycol or chitosan- NPs respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-β processing intermediates as well as neuroplasticity markers and histopathological examination were assessed. Results: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands toward AChE and Aβ42 formation and significantly down regulated Tau, iNOS and BACE gene expression in rats’ hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-β toxicity in addition to the improvement of the neuroplasticity markers. Conclusions: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake which need more investigation in future work.

scholarly journals Calycosin-7-O-β-D-glucoside Attenuates OGD/R-Induced Damage by Preventing Oxidative Stress and Neuronal Apoptosis via the SIRT1/FOXO1/PGC-1α Pathway in HT22 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Xiangli Yan ◽  
Aiming Yu ◽  
Haozhen Zheng ◽  
Shengxin Wang ◽  
Yingying He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Pathological Process ◽  
Neuroprotective Effects ◽  
Ht22 Cells ◽  
Positive Effects ◽  
Antioxidant Stress

Neuronal apoptosis induced by oxidative stress is a major pathological process that occurs after cerebral ischemia-reperfusion. Calycosin-7-O-β-D-glucoside (CG) is a representative component of isoflavones in Radix Astragali (RA). Previous studies have shown that CG has potential neuroprotective effects. However, whether CG alleviates neuronal apoptosis through antioxidant stress after ischemia-reperfusion remains unknown. To investigate the positive effects of CG on oxidative stress and apoptosis of neurons, we simulated the ischemia-reperfusion process in vitro using an immortalized hippocampal neuron cell line (HT22) and oxygen-glucose deprivation/reperfusion (OGD/R) model. CG significantly improved cell viability and reduced oxidative stress and neuronal apoptosis. In addition, CG treatment upregulated the expression of SIRT1, FOXO1, PGC-1α, and Bcl-2 and downregulated the expression of Bax. In summary, our findings indicate that CG alleviates OGD/R-induced damage via the SIRT1/FOXO1/PGC-1α signaling pathway. Thus, CG maybe a promising therapeutic candidate for brain injury associated with ischemic stroke.

scholarly journals Patients with Gaucher disease display systemic oxidative stress dependent on therapy status

2020 ◽  
Vol 25 ◽  
pp. 100667
Author(s):  
Reena V. Kartha ◽  
Marcia R. Terluk ◽  
Roland Brown ◽  
Abigail Travis ◽  
Usha R. Mishra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gaucher Disease ◽  
Systemic Oxidative Stress ◽  
Stress Dependent

scholarly journals Melatonin and Microglia

2021 ◽  
Vol 22 (15) ◽  
pp. 8296
Author(s):  
Rüdiger Hardeland
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Signal Transduction ◽  
Endothelial Cells ◽  
Bacterial Infections ◽  
Melatonin Receptors ◽  
Sterile Inflammation ◽  
High Complexity ◽  
Anti Inflammatory ◽  
Multiple Signaling

Melatonin interacts in multiple ways with microglia, both directly and, via routes of crosstalk with astrocytes and neurons, indirectly. These effects of melatonin are of relevance in terms of antioxidative protection, not only concerning free-radical detoxification, but also in prevention of processes that cause, promote, or propagate oxidative stress and neurodegeneration, such as overexcitation, toxicological insults, viral and bacterial infections, and sterile inflammation of different grades. The immunological interplay in the CNS, with microglia playing a central role, is of high complexity and includes signaling toward endothelial cells and other leukocytes by cytokines, chemokines, nitric oxide, and eikosanoids. Melatonin interferes with these processes in multiple signaling routes and steps. In addition to canonical signal transduction by MT1 and MT2 melatonin receptors, secondary and tertiary signaling is of relevance and has to be considered, e.g., via the upregulation of sirtuins and the modulation of pro- and anti-inflammatory microRNAs. Many details concerning the modulation of macrophage functionality by melatonin are obviously also applicable to microglial cells. Of particular interest is the polarization toward M2 subtypes instead of M1, i.e., in favor of being anti-inflammatory at the expense of proinflammatory activities, which is well-documented in macrophages but also applies to microglia.

scholarly journals IκBα targeting promotes oxidative stress-dependent cell death

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Giovanna Carrà ◽  
Giuseppe Ermondi ◽  
Chiara Riganti ◽  
Luisella Righi ◽  
Giulia Caron ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Fate ◽  
Protein Interactions ◽  
In Silico ◽  
Inverse Correlation ◽  
Ros Production ◽  
Gene Encoding ◽  
Specific Expression ◽  
Novel Approach ◽  
Stress Dependent

Abstract Background Oxidative stress is a hallmark of many cancers. The increment in reactive oxygen species (ROS), resulting from an increased mitochondrial respiration, is the major cause of oxidative stress. Cell fate is known to be intricately linked to the amount of ROS produced. The direct generation of ROS is also one of the mechanisms exploited by common anticancer therapies, such as chemotherapy. Methods We assessed the role of NFKBIA with various approaches, including in silico analyses, RNA-silencing and xenotransplantation. Western blot analyses, immunohistochemistry and RT-qPCR were used to detect the expression of specific proteins and genes. Immunoprecipitation and pull-down experiments were used to evaluate protein-protein interactions. Results Here, by using an in silico approach, following the identification of NFKBIA (the gene encoding IκBα) amplification in various cancers, we described an inverse correlation between IκBα, oxidative metabolism, and ROS production in lung cancer. Furthermore, we showed that novel IκBα targeting compounds combined with cisplatin treatment promote an increase in ROS beyond the tolerated threshold, thus causing death by oxytosis. Conclusions NFKBIA amplification and IκBα overexpression identify a unique cancer subtype associated with specific expression profile and metabolic signatures. Through p65-NFKB regulation, IκBα overexpression favors metabolic rewiring of cancer cells and distinct susceptibility to cisplatin. Lastly, we have developed a novel approach to disrupt IκBα/p65 interaction, restoring p65-mediated apoptotic responses to cisplatin due to mitochondria deregulation and ROS-production.

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