scholarly journals Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity

2021 ◽  
Vol 22 (10) ◽  
pp. 5347
Author(s):  
Ching-Hsuan Chou ◽  
Chia-Ron Yang
Keyword(s):  
Western Blotting ◽  
Okadaic Acid ◽  
Therapeutic Potential ◽  
Glycogen Synthase ◽  
Neuroprotective Effect ◽  
Brain Slices ◽  
Neuronal Cell ◽  
Tau Phosphorylation ◽  
Mitogen Activated Protein Kinase ◽  
Tau Aggregation

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease, and it manifests as progressive memory loss and cognitive decline. However, there are no effective therapies for AD, which is an urgent problem to solve. Evodiamine, one of the main bioactive ingredients of Evodia rutaecarpa, has been reported to ameliorate blood–brain barrier (BBB) permeability and improve cognitive impairment in ischemia and AD mouse models. However, whether evodiamine alleviates tauopathy remains unclear. This study aimed to examine whether evodiamine ameliorates tau phosphorylation and cognitive deficits in AD models. Methods: A protein phosphatase 2A inhibitor, okadaic acid (OA), was used to induce tau phosphorylation to mimic AD-like models in neuronal cells. Protein expression and cell apoptosis were detected using Western blotting and flow cytometry, respectively. Spatial memory/cognition was assessed using water maze, passive avoidance tests, and magnetic resonance imaging assay in OA-induced mice models, and brain slices were evaluated further by immunohistochemistry. Results: The results showed that evodiamine significantly reduced the expression of phosphor-tau, and further decreased tau aggregation and neuronal cell death in response to OA treatment. This inhibition was found to be via the inhibition of glycogen synthase kinase 3β, cyclin-dependent kinase 5, and mitogen-activated protein kinase pathways. In vivo results indicated that evodiamine treatment ameliorated learning and memory impairments in mice, whereas Western blotting and immunohistochemical analysis of the mouse brain also confirmed the neuroprotective effects of evodiamine. Conclusions: Evodiamine can decrease the neurotoxicity of tau aggregation and exhibit a neuroprotective effect. Our results demonstrate that evodiamine has a therapeutic potential for AD treatment.

scholarly journals Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 545
Author(s):  
Giuseppe Abbruzzese ◽  
Javier Morón-Oset ◽  
Sabela Díaz-Castroverde ◽  
Nuria García-Font ◽  
Cesáreo Roncero ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Therapeutic Potential ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Mitogen Activated Protein Kinase ◽  
Neuroprotective Effects ◽  
Signaling Mechanisms ◽  
Ribosomal S6 Kinase

Phytoestrogens can have a neuroprotective effect towards ischemia-reperfusion-induced neuronal damage. However, their mechanism of action has not been well described. In this work, we investigate the type of neuronal cell death induced by oxygen and glucose deprivation (OGD) and resupply (OGDR) and pinpoint some of the signaling mechanisms whereby the neuroprotective effects of phytoestrogens occur in these conditions. First, we found that autophagy initiation affords neuronal protection upon neuronal damage induced by OGD and OGDR. The mammalian target of rapamycin/ribosomal S6 kinase (mTOR/S6K) pathway is blocked in these conditions, and we provide evidence that this is mediated by modulation of both the 5′ AMP-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathways. These are dampened up or down, respectively, under OGDR-induced neuronal damage. In contrast, the MAPK-Erk kinase/extracellular signal-regulated kinase (MEK/ERK) pathway is increased under these conditions. Regarding the pathways affected by phytoestrogens, we show that their protective properties require autophagy initiation, but at later stages, they decrease mitogen-activated protein kinase (MAPK) and AMPK activation and increase mTOR/S6K activation. Collectively, our results put forward a novel mode of action where phytoestrogens play a dual role in the regulation of autophagy by acting as autophagy initiation enhancers when autophagy is a neuroprotective and pro-survival mechanism, and as autophagy initiation inhibitors when autophagy is a pro-death mechanism. Finally, our results support the therapeutic potential of phytoestrogens in brain ischemia by modulating autophagy.

scholarly journals Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus

2010 ◽  
Vol 205 (3) ◽  
pp. 263-270 ◽  
Author(s):  
Jiyeon Lee ◽  
Eunjin Lim ◽  
Yumi Kim ◽  
Endan Li ◽  
Seungjoon Park
Keyword(s):  
Cell Death ◽  
Kainic Acid ◽  
Hippocampal Neurons ◽  
Therapeutic Potential ◽  
Excitatory Amino Acid ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Proinflammatory Mediators ◽  
Hippocampal Neurodegeneration

Ghrelin is an endogenous ligand for GH secretagogue receptor type 1a (GHSR1a), and is produced and released mainly from the stomach. It has been recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. Kainic acid (KA), an excitatory amino acid l-glutamate analog, causes neuronal death in the hippocampus; previous studies suggest that activated microglia and astrocytes actively participate in the pathogenesis of KA-induced hippocampal neurodegeneration. However, it is unclear whether ghrelin has neuroprotective effect in KA-induced hippocampal neurodegeneration. I.p. injection of KA produced typical neuronal cell death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic administration of ghrelin significantly attenuated KA-induced neuronal cell death in these regions through the activation of GHSR1a. Ghrelin prevents KA-induced activation of microglia and astrocytes, and the expression of proinflammatory mediators tumor necrosis factor α, interleukin-1β, and cyclooxygenase-2. The inhibitory effect of ghrelin on the activation of microglia and astrocytes appears to be associated with the inhibition of matrix metalloproteinase-3 expression in damaged hippocampal neurons. Our data suggest that ghrelin has a therapeutic potential for suppressing KA-induced pathogenesis in the brain.

scholarly journals Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro

2021 ◽  
Vol 22 (21) ◽  
pp. 11484
Author(s):  
Masatoshi Inden ◽  
Ayaka Takagi ◽  
Hazuki Kitai ◽  
Taisei Ito ◽  
Hisaka Kurita ◽  
...  
Keyword(s):  
Amyloid Fibril ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Lewy Bodies ◽  
Neuronal Cell ◽  
Therapeutic Agents ◽  
Amyloid Fibril Formation ◽  
Transcription Factor Eb

Aggregation of α-synuclein (α-Syn) is implicated in the pathogenesis of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Therefore, the removal of α-Syn aggregation could lead to the development of many new therapeutic agents for neurodegenerative diseases. In the present study, we succeeded in generating a new α-Syn stably expressing cell line using a piggyBac transposon system to investigate the neuroprotective effect of the flavonoid kaempferol on α-Syn toxicity. We found that kaempferol provided significant protection against α-Syn-related neurotoxicity. Furthermore, kaempferol induced autophagy through an increase in the biogenesis of lysosomes by inducing the expression of transcription factor EB and reducing the accumulation of α-Syn; thus, kaempferol prevented neuronal cell death. Moreover, kaempferol directly blocked the amyloid fibril formation of α-Syn. These results support the therapeutic potential of kaempferol in diseases such as synucleinopathies that are characterized by α-Syn aggregates.

scholarly journals Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-30 ◽  
Author(s):  
Nur Shafika Mohd Sairazi ◽  
K. N. S. Sirajudeen
Keyword(s):  
Cell Death ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Bioactive Compounds ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuronal Structure ◽  
And Function

In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.

scholarly journals NMDA Reduces Tau Phosphorylation in Rat Hippocampal Slices by Targeting NR2A Receptors, GSK3β, and PKC Activities

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Audrée De Montigny ◽  
Ismaël Elhiri ◽  
Julie Allyson ◽  
Michel Cyr ◽  
Guy Massicotte
Keyword(s):  
Nmda Receptor ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Hippocampal Slices ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Receptor Activation ◽  
Tau Phosphorylation ◽  
Cell Death Mechanisms ◽  
Nmda Receptor Activation

The molecular mechanisms that regulate Tau phosphorylation are complex and currently incompletely understood. In the present study, pharmacological inhibitors were deployed to investigate potential processes by which the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors modulates Tau phosphorylation in rat hippocampal slices. Our results demonstrated that Tau phosphorylation at Ser199-202 residues was decreased in NMDA-treated hippocampal slices, an effect that was not reproduced at Ser262 and Ser404 epitopes. NMDA-induced reduction of Tau phosphorylation at Ser199-202 was further promoted when NR2A-containing receptors were pharmacologically isolated and were completely abrogated by the NR2A receptor antagonist NVP-AAM077. Compared with nontreated slices, we observed that NMDA receptor activation was reflected in high Ser9 and low Tyr216 phosphorylation of glycogen synthase kinase-3 beta (GSK3β), suggesting that NMDA receptor activation might diminish Tau phosphorylation via a pathway involving GSK3βinhibition. Accordingly, we found that GSK3βinactivation by a protein kinase C- (PKC-) dependent mechanism is involved in the NMDA-induced reduction of Tau phosphorylation at Ser199-202 epitopes. Taken together, these data indicate that NR2A receptor activation may be important in limiting Tau phosphorylation by a PKC/GSK3βpathway and strengthen the idea that these receptors might act as an important molecular device counteracting neuronal cell death mechanisms in various pathological conditions.

scholarly journals p63α and γ Induce TAU Phosphorylation in Cultured Mammalian Cells

2010 ◽  
Vol 4 ◽  
pp. JEN.S6295
Author(s):  
Claudie Hooper ◽  
Reem Soliman ◽  
Simon Lovestone ◽  
Richard Killick
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Kinase ◽  
Mammalian Cells ◽  
Neuronal Development ◽  
Glycogen Synthase ◽  
Tau Phosphorylation ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Here we show by western blotting that transcriptionally active isoforms of p63 (p63α and p63γ) induce the phosphorylation of human 2N4R tau at the tau-1/AT8 epitope in HEK293a cells; a phospho-epitope increased in Alzheimer's disease. Confocal microscopy shows that tau and p63α are spatially separated intracellularly. Tau was found in the cytoskeletal compartment, whilst p63α was located in the nucleus, indicating that the effects of p63 on tau phosphorylation are indirectly mediated. Tau phosphorylation occurred independently of the known tau kinases, protein kinase C delta (PKCδ), c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), glycogen synthase kinase 3 (GSK3), v-akt murine thymoma viral oncogene homolog (AKT) and cyclin-dependent kinase 5 (Cdk5) and the tau protein phosphatases (PP), PP1 and PP2A-Aα/β. Considering that p63 and tau are both associated with developmental processes, these findings have ramifications for neuronal development and synaptic plasticity and also neurodegenerative diseases such as Alzheimer's disease and other tauopathies.

scholarly journals New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation, Neurodegeneration, and Neuroprotection

2018 ◽  
Vol 8 (2) ◽  
pp. 33 ◽  
Author(s):  
Azizul Haque ◽  
Rachel Polcyn ◽  
Denise Matzelle ◽  
Naren L. Banik
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuron Specific Enolase ◽  
Neuronal Cell ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Specific Marker ◽  
Cord Injury

Neurodegeneration is a complex process that leads to irreversible neuronal damage and death in spinal cord injury (SCI) and various neurodegenerative diseases, which are serious, debilitating conditions. Despite exhaustive research, the cause of neuronal damage in these degenerative disorders is not completely understood. Elevation of cell surface α-enolase activates various inflammatory pathways, including the production of pro-inflammatory cytokines, chemokines, and some growth factors that are detrimental to neuronal cells. While α-enolase is present in all neurological tissues, it can also be converted to neuron specific enolase (NSE). NSE is a glycolytic enzyme found in neuronal and neuroendocrine tissues that may play a dual role in promoting both neuroinflammation and neuroprotection in SCI and other neurodegenerative events. Elevated NSE can promote ECM degradation, inflammatory glial cell proliferation, and actin remodeling, thereby affecting migration of activated macrophages and microglia to the injury site and promoting neuronal cell death. Thus, NSE could be a reliable, quantitative, and specific marker of neuronal injury. Depending on the injury, disease, and microenvironment, NSE may also show neurotrophic function as it controls neuronal survival, differentiation, and neurite regeneration via activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways. This review discusses possible implications of NSE expression and activity in neuroinflammation, neurodegeneration, and neuroprotection in SCI and various neurodegenerative diseases for prognostic and therapeutic potential.

scholarly journals The neurotrophic and neuroprotective effects of psychotropic agents

2009 ◽  
Vol 11 (3) ◽  
pp. 333-348 ◽  
Keyword(s):  
Neurodegenerative Diseases ◽  
Animal Studies ◽  
Therapeutic Potential ◽  
Glycogen Synthase ◽  
B Cell Lymphoma ◽  
Brain Regions ◽  
Mood Stabilizers ◽  
Mitogen Activated Protein Kinase ◽  
Neuroprotective Effects ◽  
Psychotropic Agents

Accumulating evidence suggests that psychotropic agents such as mood stabilizers, antidepressants, and antipsychotics realize their neurotrophic/neuroprotective effects by activating the mitogen activated protein kinase/extracellular signal-related kinase, PI3-kinase, and wingless/glycogen synthase kinase (GSK) 3 signaling pathways. These agents also upregulate the expression of trophic/protective molecules such as brain-derived neurotrophic factor, nerve growth factor, B-cell lymphoma 2, serine-threonine kinase, and Bcl-2 associated athanogene 1, and inactivate proapoptotic molecules such as GSK-3. They also promote neurogenesis and are protective in models of neurodegenerative diseases and ischemia. Most if not all, of this evidence was collected from animal studies that used clinically relevant treatment regimens. Furthermore, human imaging studies have found that these agents increase the volume and density of brain tissue, as well as levels of N-acetyl aspartate and glutamate in selected brain regions. Taken together, these data suggest that the neurotrophic/neuroprotective effects of these agents have broad therapeutic potential in the treatment; not only of mood disorders and schizophrenia, but also neurodegenerative diseases and ischemia.

scholarly journals Momordica charantia L. Extract Protects Hippocampal Neuronal Cells against PAHs-Induced Neurotoxicity: Possible Active Constituents Include Stigmasterol and Vitamin E

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2368
Author(s):  
Nattaporn Pattarachotanant ◽  
Anchalee Prasansuklab ◽  
Tewin Tencomnao
Keyword(s):  
Vitamin E ◽  
In Silico ◽  
Neuroprotective Effect ◽  
Neuronal Cell ◽  
In Silico Analysis ◽  
Momordica Charantia ◽  
Mitogen Activated Protein Kinase ◽  
Active Components ◽  
Neuroprotective Effects ◽  
Silico Analysis

Polycyclic aromatic hydrocarbons (PAHs) have been recognized to cause neurobehavioral dysfunctions and disorder of cognition and behavioral patterns in childhood. Momordica charantia L. (MC) has been widely known for its nutraceutical and health-promoting properties. To date, the effect of MC for the prevention and handling of PAHs-induced neurotoxicity has not been reported. In the current study, the neuroprotective effects of MC and its underlying mechanisms were investigated in mouse hippocampal neuronal cell line (HT22); moreover, in silico analysis was performed with the phytochemicals MC to decipher their potential function as neuroprotectants. MC was demonstrated to possess neuroprotective effect by reducing reactive oxygen species’ (ROS’) production and down-regulating cyclin D1, p53, and p38 mitogen-activated protein kinase (MAPK) protein expressions, resulting in the inhibition of cell apoptosis and the normalization of cell cycle progression. Additionally, 28 phytochemicals of MC and their competence on inhibiting cytochrome P450 (CYP: CYP1A1, CYP1A2, and CYP1B1) functions were resolved. In silico analysis of vitamin E and stigmasterol revealed that their binding to either CYP1A1 or CYP1A2 was more efficient than the binding of each positive control (alizarin or purpurin). Together, MC is potentially an interesting neuroprotectant including vitamin E and stigmasterol as probable active components for the prevention for PAHs-induced neurotoxicity.

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