scholarly journals Microbial Tyrosinase: Biochemical, Molecular Properties and Pharmaceutical Applications

2021 ◽  
Vol 14 (3) ◽  
pp. 1281-1295
Author(s):  
Ashraf S.A. El-Sayed ◽  
Hanaa Salah Maamoun ◽  
Gamal H. Rabie ◽  
Ibrahim Shaker ◽  
Bothaina A. Alaidaroos ◽  
...  
Keyword(s):  
Cell Death ◽  
Oxidation Reaction ◽  
Neuronal Damage ◽  
Tyrosinase Activity ◽  
Molecular Properties ◽  
Synthetic Compounds ◽  
Pharmaceutical Applications ◽  
Parkinson’S Diseases ◽  
Tyrosine Hydroxylation ◽  
Different Sources

Tyrosinase is a copper-containing monooxygenase involved in thecatalysis of the hydroxylation and oxidation reaction of monophenols and diphenols, respectively, into O-quinones intermediates. Tyrosinase is mainly involved in melanogenesis via two reactions. Firstly, 3,4-dihydroxyphenylalanine is produced through tyrosine hydroxylation the nit oxidized into dopaquinone, and finally gives melanin. However, dopaquinones can results in neuronal damage and cell death through the excessive production, suggesting that tyrosinase may be implanted in the formation human brain’s neuromelanin and association with Parkinson’s diseases. Thus, down regulating the melanin pigments and its intermediates by inhibiting tyrosinase activity is the major pharmaceutical challenge to prevent hyperpigmentation, in addition to therapy of neuromelanin disorders. Thus, this review has been focused on exploring the biochemical and molecular properties of tyrosinase from different sources and its potential inhibition with different natural and synthetic compounds.

scholarly journals TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?

2004 ◽  
Vol 1 (3) ◽  
pp. 263-273 ◽  
Author(s):  
DMITRI LEONOUDAKIS ◽  
STEVEN P. BRAITHWAITE ◽  
MICHAEL S. BEATTIE ◽  
ERIC C. BEATTIE
Keyword(s):  
Cell Death ◽  
Inflammatory Response ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cell Types ◽  
Synaptic Function ◽  
Ampar Trafficking ◽  
Novel Target

Injury and disease in the CNS increases the amount of tumor necrosis factor α (TNFα) that neurons are exposed to. This cytokine is central to the inflammatory response that occurs after injury and during prolonged CNS disease, and contributes to the process of neuronal cell death. Previous studies have addressed how long-term apoptotic-signaling pathways that are initiated by TNFα might influence these processes, but the effects of inflammation on neurons and synaptic function in the timescale of minutes after exposure are largely unexplored. Our published studies examining the effect of TNFα on trafficking of AMPA-type glutamate receptors (AMPARs) in hippocampal neurons demonstrate that glial-derived TNFα causes a rapid (<15 minute) increase in the number of neuronal, surface-localized, synaptic AMPARs leading to an increase in synaptic strength. This indicates that TNFα-signal transduction acts to facilitate increased surface localization of AMPARs from internal postsynaptic stores. Importantly, an excess of surface localized AMPARs might predispose the neuron to glutamate-mediated excitotoxicity and excessive intracellular calcium concentrations, leading to cell death. This suggests a new mechanism for excitotoxic TNFα-induced neuronal death that is initiated minutes after neurons are exposed to the products of the inflammatory response.Here we review the importance of AMPAR trafficking in normal neuronal function and how abnormalities that are mediated by glial-derived cytokines such as TNFα can be central in causing neuronal disorders. We have further investigated the effects of TNFα on different neuronal cell types and present new data from cortical and hippocampal neurons in culture. Finally, we have expanded our investigation of the temporal profile of the action of this cytokine relevant to neuronal damage. We conclude that TNFα-mediated effects on AMPAR trafficking are common in diverse neuronal cell types and very rapid in their onset. The abnormal AMPAR trafficking elicited by TNFα might present a novel target to aid the development of new neuroprotective drugs.

scholarly journals Neurotoxic Effect of Ethanolic Extract of Propolis in the Presence of Copper Ions is Mediated through Enhanced Production of ROS and Stimulation of Caspase-3/7 Activity

Toxins ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 273 ◽  
Author(s):  
Vedrana Radovanović ◽  
Josipa Vlainić ◽  
Nikolina Hanžić ◽  
Petra Ukić ◽  
Nada Oršolić ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ethanolic Extract ◽  
Mitogen Activated Protein Kinase ◽  
Enhanced Production ◽  
Toxicological Studies ◽  
Ethanolic Extract Of Propolis

Elevated amounts of copper are considered to be contributing factor in the progression of neurodegenerative diseases as they promote oxidative stress conditions. The aim of our study was to examine the effects of ethanolic extract of propolis (EEP) against copper-induced neuronal damage. In cultured P19 neuronal cells, EEP exacerbated copper-provoked neuronal cell death by increasing the generation of reactive oxygen species (ROS) and through the activation of caspase-3/7 activity. EEP augmented copper-induced up-regulation of p53 and Bax mRNA expressions. Neurotoxic effects of EEP were accompanied by a strong induction of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression and decrease in the expression of c-fos mRNA. SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK) prevented detrimental effects of EEP, whereas SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), exacerbated EEP-induced neuronal cell death. Quercetin, a polyphenolic nutraceutical, which is usually present in propolis, was also able to exacerbate copper-induced neuronal death. Our data indicates a pro-oxidative and apoptotic mode of EEP action in the presence of excess copper, wherein ROS/p53/p38 interactions play an important role in death cascades. Our study also pointed out that detailed pharmacological and toxicological studies must be carried out for propolis and other dietary supplements in order to fully recognize the potential adverse effects in specific conditions.

Brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats

1996 ◽  
Vol 80 (2) ◽  
pp. 680-684 ◽  
Author(s):  
T. Y. Kao ◽  
M. T. Lin
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Survival Time ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Serotonin Release ◽  
Brain Serotonin ◽  
Serotonin Depletion

To explore the importance of brain serotonin (5-hydroxytryptamine) in the heatstroke-induced cerebral ischemia and neuronal injury, we evaluated the effects of heatstroke on brain serotonin release, survival time, cerebral hemodynamic changes, and neuronal cell damage in rats with or without brain serotonin depletion produced by 5,7-dihydroxytryptamine. In vivo voltammetry was used to measure changes in extracellular concentrations of serotonin in the anterior hypothalamus, striatum, and frontal cortex. After the onset of heatstroke, rats without brain serotonin depletion displayed hyperthermia, decreased mean arterial pressure, increased intracranial pressure, decreased cerebral perfusion pressure, decreased cerebral blood flow, increased cerebral serotonin release, and increased cerebral neuronal damage compared with those of normothermic control rats. However, when the cerebral serotonin system was destroyed by 5,7-dihydroxytryptamine, the heatstroke-induced arterial hypotension, intracranial hypertension, ischemic damage to the brain, and elevated cerebral serotonin release were reduced. In addition, the survival time of the heatstroke rats was prolonged after the depletion of brain serotonin. The data indicate that brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats.

Sodium Azide Induced Neuronal Damage In Vitro: Evidence for Non-Apoptotic Cell Death

2008 ◽  
Vol 34 (5) ◽  
pp. 909-916 ◽  
Author(s):  
Rita Selvatici ◽  
Maurizio Previati ◽  
Silvia Marino ◽  
Luca Marani ◽  
Sofia Falzarano ◽  
...  
Keyword(s):  
Cell Death ◽  
Sodium Azide ◽  
Neuronal Damage ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death

scholarly journals Oxidative Damage to the Endoplasmic Reticulum is Implicated in Ischemic Neuronal Cell Death

2003 ◽  
Vol 23 (10) ◽  
pp. 1117-1128 ◽  
Author(s):  
Takeshi Hayashi ◽  
Atsushi Saito ◽  
Shuzo Okuno ◽  
Michel Ferrand-Drake ◽  
Robert L Dodd ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Protein Modification ◽  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Transgenic Animals ◽  
Initiation Factor

The endoplasmic reticulum (ER), which plays important roles in apoptosis, is susceptible to oxidative stress. Because reactive oxygen species (ROS) are robustly produced in the ischemic brain, ER damage by ROS may be implicated in ischemic neuronal cell death. We induced global brain ischemia on wild-type and copper/zinc superoxide dismutase (SOD1) transgenic rats and compared ER stress and neuronal damage. Phosphorylated forms of eukaryotic initiation factor 2α (eIF2α) and RNA-dependent protein kinase-like ER eIF2α kinase (PERK), both of which play active roles in apoptosis, were increased in hippocampal CA1 neurons after ischemia but to a lesser degree in the transgenic animals. This finding, together with the finding that the transgenic animals showed decreased neuronal degeneration, indicates that oxidative ER damage is involved in ischemic neuronal cell death. To elucidate the mechanisms of ER damage by ROS, we analyzed glucose-regulated protein 78 (GRP78) binding with PERK and oxidative ER protein modification. The proteins were oxidatively modified and stagnated in the ER lumen, and GRP78 was detached from PERK by ischemia, all of which were attenuated by SOD1 overexpression. We propose that ROS attack and modify ER proteins and elicit ER stress response, which results in neuronal cell death.

scholarly journals Adrenergic signaling in muscularis macrophages limits neuronal death following enteric infection

2019 ◽  
Author(s):  
Fanny Matheis ◽  
Paul A. Muller ◽  
Christina Graves ◽  
Ilana Gabanyi ◽  
Zachary J. Kerner ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Gastrointestinal Symptoms ◽  
Neuronal Cell ◽  
Neuronal Loss ◽  
Enteric Infection ◽  
Loss Of Function ◽  
Arginase 1 ◽  
Irritable Bowel

SummaryEnteric–associated neurons (EANs) are closely associated with immune cells and continuously monitor and modulate homeostatic intestinal functions, including motility. Bidirectional interactions between immune and neuronal cells are altered during disease processes such as neurodegeneration or irritable bowel syndrome. We investigated how infection-induced inflammation affects intrinsic EANs and the role of intestinalmuscularismacrophages (MMs) in this process. Using murine model of bacterial infection, we observed long-term gastrointestinal symptoms including reduced motility and subtype-specific neuronal loss. Neuronal-specific translational–profiling uncovered a caspase 11–dependent EAN cell–death mechanism induced by enteric infections. MMs responded to luminal infection by upregulating a neuroprotective program; gain– and loss–of-function experiments indicated that β2-adrenergic receptor (β2-AR) signaling in MMs mediates neuronal protection during infection via an arginase 1-polyamine axis. Our results identify a mechanism of neuronal cell death post–infection and point to a role for tissue–resident MMs in limiting neuronal damage.

scholarly journals Programmed Cell Death Protein 1 Blockade Reduces Glycogen Synthase Kinase 3β Activity and Tau Hyperphosphorylation in Alzheimer’s Disease Mouse Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Yulian Zou ◽  
Chen-Ling Gan ◽  
Zhiming Xin ◽  
Hai-Tao Zhang ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Mouse Models ◽  
Glycogen Synthase ◽  
Neuronal Damage ◽  
Amyloid Β ◽  
Glycogen Synthase Kinase ◽  
Tau Hyperphosphorylation

Alzheimer’s disease (AD) is a central nervous system degenerative disease, with no effective treatment to date. Administration of immune checkpoint inhibitors significantly reduces neuronal damage and tau hyperphosphorylation in AD, but the specific mechanism is unclear. Here, we found that programmed cell death-receptor 1 (PD1) and its ligand PDL1 were induced by an intracerebroventricular injection of amyloid-β; they were significantly upregulated in the brains of APP/PS1, 5×FAD mice and in SH-SY5Y-APP cell line compared with control. The PD1 and PDL1 levels positively correlated with the glycogen synthase kinase 3 beta (GSK3β) activity in various AD mouse models, and the PDL1-GSK3β immune complex was found in the brain. The application of PD1-blocking antibody reduced tau hyperphosphorylation and GSK3β activity and prevented memory impairments. Mechanistically, we identified PD1 as a critical regulator of GSK3β activity. These results suggest that the immune regulation of the PD1/PDL1 axis is closely involved in AD.

Three diachronic sources for the development of -erei-based synthetic compounds in German

2020 ◽  
Vol 13 (3) ◽  
pp. 347-370
Author(s):  
Martina Werner
Keyword(s):  
Low Frequency ◽  
Word Formation ◽  
Book Reading ◽  
German Language ◽  
Middle High German ◽  
Old High German ◽  
Synthetic Compounds ◽  
Free Spirit ◽  
History Of ◽  
Different Sources

This article investigates the historical development of synthetic compounds with the suffix -erei, such as German Buchleserei ‘book reading’. Synthetic compounding has been attested in older language stages of German, as in Old High German kirihwihî ‘church consecration’ or Middle High German bluotspîunge ‘blood spitting’. In the history of the German language, synthetic compounds are the last step in the development of a nominalizing suffix. Suffixes attach first to simplex bases (such as German Leserei ‘reading’), and only afterwards can they form synthetic compounds with a compound base (such as Bücherleserei ‘reading of books’). The development of verbal synthetic compounding results from three different sources: a) a suffixal pattern based on compound nominals (such as exocentric Freigeist ‘free spirit’ becomes Freigeisterei ‘free spiritedness’), where the pattern develops the ability to nominalize VPs (such as Nichtstuerei ‘doing nothing’); b) root compounds which develop the ability to take a deverbal head suffixed by -erei (such as Venus–Nascherey ‘Venusian nibbling’); and c) low-frequency - erei-compounds which originate from inherited idiomatic compound verbs (such as Ehebrecherei ‘adultery’, lit. ‘marriage-breakery’ > ehebrechen (V) ‘to commit adultery’, lit. ‘to marriage-break’). The paper delineates the three developments for different word formation types which lead to the morphological distribution of present-day German.

scholarly journals P27 Protects Neurons from Ischemic Damage by Suppressing Oxidative Stress and Increasing Autophagy in the Hippocampus

2020 ◽  
Vol 21 (24) ◽  
pp. 9496
Author(s):  
Woosuk Kim ◽  
Hyun Jung Kwon ◽  
Hyo Young Jung ◽  
Kyu Ri Hahn ◽  
Yeo Sung Yoon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Damage ◽  
Ischemic Damage ◽  
Dependent Manner ◽  
Membrane Phospholipids ◽  
Ht22 Cells ◽  
H2o2 Treatment ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region

p27Kip1 (p27), a well-known cell regulator, is involved in the regulation of cell death and survival. In the present study, we observed the effects of p27 against oxidative stress induced by H2O2 in HT22 cells and transient ischemia in gerbils. Tat (trans-acting activator of transcription) peptide and p27 fusion proteins were prepared to facilitate delivery into cells and across the blood-brain barrier. The tat-p27 fusion protein, rather than its control protein Control-p27, was delivered intracellularly in a concentration and incubation time-dependent manner and showed its activity in HT22 cells. The localization of the delivered Tat-p27 protein was also confirmted in the HT22 cells and hippocampus in gerbils. In addition, the optimal concentration (5 μM) of Tat-p27 was determined to protect neurons from cell death induced by 1 mM H2O2. Treatment with 5 μM Tat-p27 significantly ameliorated H2O2-induced DNA fragmentation and the formation of reactive oxygen species (ROS) in HT22 cells. Tat-p27 significantly mitigated the increase in locomotor activity a day after ischemia and neuronal damage in the hippocampal CA1 region. It also reduced the ischemia-induced membrane phospholipids and ROS formation. In addition, Tat-p27 significantly increased microtubule-associated protein 1A/1B light chain 3A/3B expression and ameliorated the H2O2 or ischemia-induced increases of p62 and decreases of beclin-1 in the HT22 cells and hippocampus. These results suggest that Tat-p27 protects neurons from oxidative or ischemic damage by reducing ROS-induced damage and by facilitating the formation of autophagosomes in hippocampal cells.

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