The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Despina Sanoudou - One of the best experts on this subject based on the ideXlab platform.
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the crocus sativus compounds trans crocin 4 and trans crocetin modulate the amyloidogenic pathway and tau misprocessing in alzheimer disease Neuronal Cell Culture models
Frontiers in Neuroscience, 2019Co-Authors: Ioanna Chalatsa, Demetrios A Arvanitis, Athina Giagini, Zeta Papadopouloudaifoti, Anthony Tsarbopoulos, Nikolaos Stavros Koulakiotis, Alexios Leandros Skaltsounis, Despina SanoudouAbstract:Crocus sativus L. natural compounds have been extensively used in traditional medicine for thousands of years. Recent research evidence is now emerging in support of its therapeutic potential for different pathologies including neurodegenerative diseases. Herein, the C. sativus L. natural compounds trans-crocin 4 and trans-crocetin were selected for in depth molecular characterization of their potentially protective effects against Alzheimer's Disease (AD), utilizing two AD Neuronal Cell Culture models (SH-SY5Y overexpressing APP and PC12 expressing hyperphosphorylated tau). Biologically relevant concentrations, ranging from 0.1 μM to 1 mM, applied for 24 h or 72 h, were well tolerated by differentiated wild type SH-SY5Y and PC12 Cells. When tested on Neuronally differentiated SH-SY5Y-APP both trans-crocin 4 and trans-crocetin had significant effects against amyloidogenic pathways. Trans-crocin 4 significantly decreased of β-secretase, a key enzyme of the amyloidogenic pathway, and APP-C99, while it decreased γ-secretases that generate toxic beta-amyloid peptides. Similarly, trans-crocetin treatment led to a reduction in β- and γ-secretases, as well as to accumulation of Cellular AβPP. When tested on the Neuronally differentiated PC12-htau Cells, both compounds proved effective in suppressing the active forms of GSK3β and ERK1/2 kinases, as well as significantly reducing total tau and tau phosphorylation. Collectively, our data demonstrate a potent effect of trans-crocin 4 and trans-crocetin in suppressing key molecular pathways of AD pathogenesis, rendering them a promising tool in the prevention and potentially the treatment of AD.
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Data_Sheet_1_The Crocus sativus Compounds trans-Crocin 4 and trans-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models.pdf
2019Co-Authors: Ioanna Chalatsa, Demetrios A Arvanitis, Athina Giagini, Anthony Tsarbopoulos, Nikolaos Stavros Koulakiotis, Alexios Leandros Skaltsounis, Zeta Papadopoulou-daifoti, Despina SanoudouAbstract:Crocus sativus L. natural compounds have been extensively used in traditional medicine for thousands of years. Recent research evidence is now emerging in support of its therapeutic potential for different pathologies including neurodegenerative diseases. Herein, the C. sativus L. natural compounds trans-crocin 4 and trans-crocetin were selected for in depth molecular characterization of their potentially protective effects against Alzheimer’s Disease (AD), utilizing two AD Neuronal Cell Culture models (SH-SY5Y overexpressing APP and PC12 expressing hyperphosphorylated tau). Biologically relevant concentrations, ranging from 0.1 μM to 1 mM, applied for 24 h or 72 h, were well tolerated by differentiated wild type SH-SY5Y and PC12 Cells. When tested on Neuronally differentiated SH-SY5Y-APP both trans-crocin 4 and trans-crocetin had significant effects against amyloidogenic pathways. Trans-crocin 4 significantly decreased of β-secretase, a key enzyme of the amyloidogenic pathway, and APP-C99, while it decreased γ-secretases that generate toxic beta-amyloid peptides. Similarly, trans-crocetin treatment led to a reduction in β- and γ-secretases, as well as to accumulation of Cellular AβPP. When tested on the Neuronally differentiated PC12-htau Cells, both compounds proved effective in suppressing the active forms of GSK3β and ERK1/2 kinases, as well as significantly reducing total tau and tau phosphorylation. Collectively, our data demonstrate a potent effect of trans-crocin 4 and trans-crocetin in suppressing key molecular pathways of AD pathogenesis, rendering them a promising tool in the prevention and potentially the treatment of AD.
Allan D Butterfield - One of the best experts on this subject based on the ideXlab platform.
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in vivo protection of synaptosomes by ferulic acid ethyl ester faee from oxidative stress mediated by 2 2 azobis 2 amidino propane dihydrochloride aaph or fe2 h2o2 insight into mechanisms of neuroprotection and relevance to oxidative stress related n
Neurochemistry International, 2006Co-Authors: Gururaj Joshi, Marzia Perluigi, Rukhsana Sultana, Ravagna Agrippino, Vittorio Calabrese, Allan D ButterfieldAbstract:Ferulic acid ethyl ester (FAEE) is an ester derivative of ferulic acid, the latter known for its anti-inflammatory and antioxidant properties. Previous studies from our laboratory have shown that ferulic acid protects synaptosomal membrane system and Neuronal Cell Culture systems against hydroxyl and peroxyl radical oxidation. FAEE is lipophilic and is able to penetrate lipid bilayer. Previous studies reported that FAEE reduces Alzheimer’s amyloid b peptide Ab(1‐42)-induced oxidative stress and cytotoxicity in Neuronal Cell Culture by direct radical scavenging and by inducing certain antioxidant proteins. In the present study we tested the hypothesis that FAEE would provide neuroprotection against free radical oxidative stress in vivo. Synaptosomes were isolated from the gerbils that were previously injected intraperitoneally (i.p.) with FAEE or DMSO and were treated with oxidants, Fe 2+ /H2O2 or 2,2-azobis(2-amidino-propane)dihydrochloride (AAPH). Synaptosomes isolated from the gerbil previously injected i.p. with FAEE and treated with Fe 2+ /H2O2 and AAPH showed significant reduction in reactive oxygen species (ROS), levels of protein carbonyl, protein bound 4-hydroxynonenal (HNE, a lipid peroxidation product), and 3-nitrotyrosine (3-NT, another marker of protein oxidation formed by reaction of tyrosine residues with peroxynitrite) compared to Fe 2+ /H2O2 or AAPH induced oxidative stress in synapotosomes isolated from the brain of gerbils that were previously injected with DMSO. The synaptosomes isolated from gerbil pre-injected with FAEE and subsequently treated with AAPH or Fe 2+ /H2O2 showed induction of heme oxygenase (HO-1) and heat shock protein 70 (HSP-70) but reduced inducible nitric oxide synthase (iNOS) levels. These results are discussed with reference to potential use of this lipophilic antioxidant phenolic compound in the treatment of oxidative stress-related neurodegenerative disorders. # 2005 Elsevier Ltd. All rights reserved.
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gamma glutamylcysteine ethyl ester protection of proteins from abeta 1 42 mediated oxidative stress in Neuronal Cell Culture a proteomics approach
Journal of Neuroscience Research, 2005Co-Authors: Debra Boydkimball, Rukhsana Sultana, Fai H Poon, Hafiz Mohmmadabdul, Bert C Lynn, Jon B Klein, Allan D ButterfieldAbstract:Protein oxidation mediated by amyloid β-peptide (1–42) (Aβ[1–42]) has been proposed to play a central role in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder associated with aging and the loss of cognitive function. The specific mechanism by which Aβ(1–42), the primary component of the senile plaque and a pathologic hallmark of AD, contributes to the oxidative damage evident in AD brain is unknown. Moreover, the specific proteins that are vulnerable to oxidative damage induced by Aβ(1–42) are unknown. Identification of such proteins could contribute to our understanding of not only the role of Aβ(1–42) in the pathogenesis of AD, but also provide insight into the mechanisms of neurodegeneration at the protein level in AD. We report the proteomic identification of two proteins found to be oxidized significantly in Neuronal Cultures treated with Aβ(1–42): 14-3-3ζ and glyceraldehyde-3-phosphate dehydrogenase. We also report that pretreatment of Neuronal Cultures with γ-glutamylcysteine ethyl ester, a compound that supplies the limiting substrate for the synthesis of glutathione and results in the upregulation of glutathione in Neuronal Cultures, protects both proteins against Aβ(1–42)-mediated protein oxidation. © 2005 Wiley-Liss, Inc.
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ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and Neuronal Cell Culture systems in vitro structure activity studies
Journal of Nutritional Biochemistry, 2002Co-Authors: Jaroslaw Kanski, Marina V Aksenova, Antonia Stoyanova, Allan D ButterfieldAbstract:In this study, free radical scavenging abilities of ferulic acid in relation to its structural characteristics were evaluated in solution, Cultured neurons, and synaptosomal systems exposed to hydroxyl and peroxyl radicals. Cultured Neuronal Cells exposed to the peroxyl radical initiator AAPH die in a dose-response manner and show elevated levels of protein carbonyls. The presence of ferulic acid or similar phenolic compounds, however, greatly reduces free radical damage in Neuronal Cell systems without causing Cell death by themselves. In addition, synaptosomal membrane systems exposed to oxidative stress by hydroxyl and peroxyl radical generators show elevated levels of oxidation as indexed by protein oxidation, lipid peroxidation, and ROS measurement. Ferulic acid greatly attenuates these changes, and its effects are far more potent than those obtained for vanillic, coumaric, and cinnamic acid treatments. Moreover, ferulic acid protects against free radical mediated changes in conformation of synaptosomal membrane proteins as monitored by EPR spin labeling techniques. The results presented in this study suggest the importance of naturally occurring antioxidants such as ferulic acid in therapeutic intervention methodology against neurodegenerative disorders such as Alzheimer's disease in which oxidative stress is implicated.
Rukhsana Sultana - One of the best experts on this subject based on the ideXlab platform.
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in vivo protection of synaptosomes by ferulic acid ethyl ester faee from oxidative stress mediated by 2 2 azobis 2 amidino propane dihydrochloride aaph or fe2 h2o2 insight into mechanisms of neuroprotection and relevance to oxidative stress related n
Neurochemistry International, 2006Co-Authors: Gururaj Joshi, Marzia Perluigi, Rukhsana Sultana, Ravagna Agrippino, Vittorio Calabrese, Allan D ButterfieldAbstract:Ferulic acid ethyl ester (FAEE) is an ester derivative of ferulic acid, the latter known for its anti-inflammatory and antioxidant properties. Previous studies from our laboratory have shown that ferulic acid protects synaptosomal membrane system and Neuronal Cell Culture systems against hydroxyl and peroxyl radical oxidation. FAEE is lipophilic and is able to penetrate lipid bilayer. Previous studies reported that FAEE reduces Alzheimer’s amyloid b peptide Ab(1‐42)-induced oxidative stress and cytotoxicity in Neuronal Cell Culture by direct radical scavenging and by inducing certain antioxidant proteins. In the present study we tested the hypothesis that FAEE would provide neuroprotection against free radical oxidative stress in vivo. Synaptosomes were isolated from the gerbils that were previously injected intraperitoneally (i.p.) with FAEE or DMSO and were treated with oxidants, Fe 2+ /H2O2 or 2,2-azobis(2-amidino-propane)dihydrochloride (AAPH). Synaptosomes isolated from the gerbil previously injected i.p. with FAEE and treated with Fe 2+ /H2O2 and AAPH showed significant reduction in reactive oxygen species (ROS), levels of protein carbonyl, protein bound 4-hydroxynonenal (HNE, a lipid peroxidation product), and 3-nitrotyrosine (3-NT, another marker of protein oxidation formed by reaction of tyrosine residues with peroxynitrite) compared to Fe 2+ /H2O2 or AAPH induced oxidative stress in synapotosomes isolated from the brain of gerbils that were previously injected with DMSO. The synaptosomes isolated from gerbil pre-injected with FAEE and subsequently treated with AAPH or Fe 2+ /H2O2 showed induction of heme oxygenase (HO-1) and heat shock protein 70 (HSP-70) but reduced inducible nitric oxide synthase (iNOS) levels. These results are discussed with reference to potential use of this lipophilic antioxidant phenolic compound in the treatment of oxidative stress-related neurodegenerative disorders. # 2005 Elsevier Ltd. All rights reserved.
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gamma glutamylcysteine ethyl ester protection of proteins from abeta 1 42 mediated oxidative stress in Neuronal Cell Culture a proteomics approach
Journal of Neuroscience Research, 2005Co-Authors: Debra Boydkimball, Rukhsana Sultana, Fai H Poon, Hafiz Mohmmadabdul, Bert C Lynn, Jon B Klein, Allan D ButterfieldAbstract:Protein oxidation mediated by amyloid β-peptide (1–42) (Aβ[1–42]) has been proposed to play a central role in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder associated with aging and the loss of cognitive function. The specific mechanism by which Aβ(1–42), the primary component of the senile plaque and a pathologic hallmark of AD, contributes to the oxidative damage evident in AD brain is unknown. Moreover, the specific proteins that are vulnerable to oxidative damage induced by Aβ(1–42) are unknown. Identification of such proteins could contribute to our understanding of not only the role of Aβ(1–42) in the pathogenesis of AD, but also provide insight into the mechanisms of neurodegeneration at the protein level in AD. We report the proteomic identification of two proteins found to be oxidized significantly in Neuronal Cultures treated with Aβ(1–42): 14-3-3ζ and glyceraldehyde-3-phosphate dehydrogenase. We also report that pretreatment of Neuronal Cultures with γ-glutamylcysteine ethyl ester, a compound that supplies the limiting substrate for the synthesis of glutathione and results in the upregulation of glutathione in Neuronal Cultures, protects both proteins against Aβ(1–42)-mediated protein oxidation. © 2005 Wiley-Liss, Inc.
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Gamma-glutamylcysteine ethyl ester protection of proteins from Abeta(1-42)-mediated oxidative stress in Neuronal Cell Culture: a proteomics approach.
Journal of Neuroscience Research, 2005Co-Authors: Debra Boyd-kimball, Rukhsana Sultana, Bert C Lynn, Jon B Klein, H. Fai Poon, Hafiz Mohmmad-abdul, D. Allan ButterfieldAbstract:: Protein oxidation mediated by amyloid beta-peptide (1-42) (Abeta[1-42]) has been proposed to play a central role in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder associated with aging and the loss of cognitive function. The specific mechanism by which Abeta(1-42), the primary component of the senile plaque and a pathologic hallmark of AD, contributes to the oxidative damage evident in AD brain is unknown. Moreover, the specific proteins that are vulnerable to oxidative damage induced by Abeta(1-42) are unknown. Identification of such proteins could contribute to our understanding of not only the role of Abeta(1-42) in the pathogenesis of AD, but also provide insight into the mechanisms of neurodegeneration at the protein level in AD. We report the proteomic identification of two proteins found to be oxidized significantly in Neuronal Cultures treated with Abeta(1-42): 14-3-3zeta and glyceraldehyde-3-phosphate dehydrogenase. We also report that pretreatment of Neuronal Cultures with gamma-glutamylcysteine ethyl ester, a compound that supplies the limiting substrate for the synthesis of glutathione and results in the upregulation of glutathione in Neuronal Cultures, protects both proteins against Abeta(1-42)-mediated protein oxidation.
Prakash V Reddy - One of the best experts on this subject based on the ideXlab platform.
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novel purine based fluoroaryl 1 2 3 triazoles as neuroprotecting agents synthesis Neuronal Cell Culture investigations and cdk5 docking studies
ChemInform, 2011Co-Authors: Nanditha Nair, Wataru Kudo, Mark Smith, Ravinder Abrol, William A Goddard, Prakash V ReddyAbstract:Key reaction in the synthesis of the title compounds (V) is a Cu(I) catalyzed azide alkyne Huisgen cycloaddition (click reaction).
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novel purine based fluoroaryl 1 2 3 triazoles as neuroprotecting agents synthesis Neuronal Cell Culture investigations and cdk5 docking studies
Bioorganic & Medicinal Chemistry Letters, 2011Co-Authors: Nanditha Nair, Wataru Kudo, Mark Smith, Ravinder Abrol, William A Goddard, Prakash V ReddyAbstract:A series of novel purine-based fluoroaryl triazoles were synthesized using the Cu(I) catalyzed 1,3-dipolar cycloaddition reactions (click reactions), and assayed for their neuroprotective effects using fluorescence electron microscopy. Among these triazoles, o-fluorophenylmetyl-triazole, 7, has comparable neuroprotective effect as that of Flavopiridol (1) and Roscovitine (2), the state of the art CDK inhibitors, against the Aβ induced neurotoxicity. These results are substantiated using computer docking methods (DarwinDock/GenDock), which predict that Roscovitine and the triazole 7 bind to the ATP-binding site of CDK5/p25 with comparable binding energies, whereas the corresponding pentafluorophenylmethyl-triazole, 9, has dramatically reduced binding energy (in accordance with its lack of neuroprotection). These combined experimental and theoretical studies support the involvement of CDK5/p25 in the Neuronal Cell cycle re-entry.
Anthony Tsarbopoulos - One of the best experts on this subject based on the ideXlab platform.
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the crocus sativus compounds trans crocin 4 and trans crocetin modulate the amyloidogenic pathway and tau misprocessing in alzheimer disease Neuronal Cell Culture models
Frontiers in Neuroscience, 2019Co-Authors: Ioanna Chalatsa, Demetrios A Arvanitis, Athina Giagini, Zeta Papadopouloudaifoti, Anthony Tsarbopoulos, Nikolaos Stavros Koulakiotis, Alexios Leandros Skaltsounis, Despina SanoudouAbstract:Crocus sativus L. natural compounds have been extensively used in traditional medicine for thousands of years. Recent research evidence is now emerging in support of its therapeutic potential for different pathologies including neurodegenerative diseases. Herein, the C. sativus L. natural compounds trans-crocin 4 and trans-crocetin were selected for in depth molecular characterization of their potentially protective effects against Alzheimer's Disease (AD), utilizing two AD Neuronal Cell Culture models (SH-SY5Y overexpressing APP and PC12 expressing hyperphosphorylated tau). Biologically relevant concentrations, ranging from 0.1 μM to 1 mM, applied for 24 h or 72 h, were well tolerated by differentiated wild type SH-SY5Y and PC12 Cells. When tested on Neuronally differentiated SH-SY5Y-APP both trans-crocin 4 and trans-crocetin had significant effects against amyloidogenic pathways. Trans-crocin 4 significantly decreased of β-secretase, a key enzyme of the amyloidogenic pathway, and APP-C99, while it decreased γ-secretases that generate toxic beta-amyloid peptides. Similarly, trans-crocetin treatment led to a reduction in β- and γ-secretases, as well as to accumulation of Cellular AβPP. When tested on the Neuronally differentiated PC12-htau Cells, both compounds proved effective in suppressing the active forms of GSK3β and ERK1/2 kinases, as well as significantly reducing total tau and tau phosphorylation. Collectively, our data demonstrate a potent effect of trans-crocin 4 and trans-crocetin in suppressing key molecular pathways of AD pathogenesis, rendering them a promising tool in the prevention and potentially the treatment of AD.
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Data_Sheet_1_The Crocus sativus Compounds trans-Crocin 4 and trans-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models.pdf
2019Co-Authors: Ioanna Chalatsa, Demetrios A Arvanitis, Athina Giagini, Anthony Tsarbopoulos, Nikolaos Stavros Koulakiotis, Alexios Leandros Skaltsounis, Zeta Papadopoulou-daifoti, Despina SanoudouAbstract:Crocus sativus L. natural compounds have been extensively used in traditional medicine for thousands of years. Recent research evidence is now emerging in support of its therapeutic potential for different pathologies including neurodegenerative diseases. Herein, the C. sativus L. natural compounds trans-crocin 4 and trans-crocetin were selected for in depth molecular characterization of their potentially protective effects against Alzheimer’s Disease (AD), utilizing two AD Neuronal Cell Culture models (SH-SY5Y overexpressing APP and PC12 expressing hyperphosphorylated tau). Biologically relevant concentrations, ranging from 0.1 μM to 1 mM, applied for 24 h or 72 h, were well tolerated by differentiated wild type SH-SY5Y and PC12 Cells. When tested on Neuronally differentiated SH-SY5Y-APP both trans-crocin 4 and trans-crocetin had significant effects against amyloidogenic pathways. Trans-crocin 4 significantly decreased of β-secretase, a key enzyme of the amyloidogenic pathway, and APP-C99, while it decreased γ-secretases that generate toxic beta-amyloid peptides. Similarly, trans-crocetin treatment led to a reduction in β- and γ-secretases, as well as to accumulation of Cellular AβPP. When tested on the Neuronally differentiated PC12-htau Cells, both compounds proved effective in suppressing the active forms of GSK3β and ERK1/2 kinases, as well as significantly reducing total tau and tau phosphorylation. Collectively, our data demonstrate a potent effect of trans-crocin 4 and trans-crocetin in suppressing key molecular pathways of AD pathogenesis, rendering them a promising tool in the prevention and potentially the treatment of AD.
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beneficial effects of sideritis scardica and cichorium spinosum against amyloidogenic pathway and tau misprocessing in alzheimer s disease Neuronal Cell Culture models
Journal of Alzheimer's Disease, 2018Co-Authors: Ioanna Chalatsa, Demetrios A Arvanitis, Eleni V Mikropoulou, Athina Giagini, Zeta Papadopouloudaifoti, Nektarios Aligiannis, Maria Halabalaki, Anthony Tsarbopoulos, Leandros SkaltsounisAbstract:Background Natural products are a significantly underutilized source of potential treatments against human disease. Alzheimer's disease (AD) is a prime example of conditions that could be amenable to such treatments as suggested by recent findings. Objective Aiming to identify novel potentially therapeutic approaches against AD, we assessed the effects of Cichorium spinosum and Sideritis scardica extracts, both distinct components of the Mediterranean diet. Methods/results After the detailed characterization of the extracts' composition using LC-HRMS methods, they were evaluated on two AD Neuronal Cell Culture models, namely the AβPP overexpressing SH-SY5Y-AβPP and the hyperphosphorylated tau expressing PC12-htau. Initially their effect on Cell viability of SH-SY5Y and PC12 Cells was examined, and subsequently their downstream effects on AβPP and tau processing pathways were investigated in the SH-SY5Y-AβPP and PC12-htau Cells. We found that the S. scardica and C. spinosum extracts have similar effects on tau, as they both significantly decrease total tau, the activation of the GSK3β, ERK1 and/or ERK2 kinases of tau, as well as tau hyperphosphorylation. Furthermore, both extracts appear to promote AβPP processing through the alpha, non-amyloidogenic pathway, albeit through partly different mechanisms. Conclusions These findings suggest that C. spinosum and S. scardica could have a notable potential in the prevention and/or treatment of AD, and merit further investigations at the in vivo level.
