The Experts below are selected from a list of 401991 Experts worldwide ranked by ideXlab platform
Mark S Hipp - One of the best experts on this subject based on the ideXlab platform.
-
multiple pathways of toxicity induced by c9orf72 dipeptide repeat aggregates and g4c2 rna in a Cellular Model
2021Co-Authors: Frederic Frottin, Manuela Perezberlanga, Ulrich F Hartl, Mark S HippAbstract:The most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia is a G4C2 repeat expansion in the C9orf72 gene. This expansion gives rise to translation of aggregating dipeptide repeat (DPR) proteins, including poly-GA as the most abundant species. However, gain of toxic function effects have been attributed to either the DPRs or the pathological G4C2 RNA. Here, we analyzed in a Cellular Model the relative toxicity of DPRs and RNA. Cytoplasmic poly-GA aggregates, generated in the absence of G4C2 RNA, interfered with nucleocytoplasmic protein transport, but had little effect on cell viability. In contrast, nuclear poly-GA was more toxic, impairing nucleolar protein quality control and protein biosynthesis. Production of the G4C2 RNA strongly reduced viability independent of DPR translation and caused pronounced inhibition of nuclear mRNA export and protein biogenesis. Thus, while the toxic effects of G4C2 RNA predominate in the Cellular Model used, DPRs exert additive effects that may contribute to pathology.
-
multiple pathways of toxicity induced by c9orf72 dipeptide repeat aggregates and g4c2 rna in a Cellular Model
2020Co-Authors: Frederic Frottin, Manuela Perezberlanga, Ulrich F Hartl, Mark S HippAbstract:Abstract The most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia is a G4C2 repeat expansion in the C9orf72 gene. This expansion gives rise to translation of aggregating dipeptide repeat (DPR) proteins, including poly-GA as the most abundant species. However, gain of toxic function effects have been attributed to either the DPRs or the pathological G4C2 RNA. Here we analyzed in a Cellular Model the relative toxicity of DPRs and RNA. Cytoplasmic poly-GA aggregates, generated in the absence of G4C2 RNA, interfered with nucleocytoplasmic protein transport, but had little effect on cell viability. In contrast, nuclear poly-GA was more toxic, impairing nucleolar protein quality control and protein biosynthesis. Production of the G4C2 RNA strongly reduced viability independent of DPR translation and caused pronounced inhibition of nuclear mRNA export and protein biogenesis. Thus, while the toxic effects of G4C2 RNA predominate, DPRs exert additive effects that may contribute to pathology.
-
heat shock response activation exacerbates inclusion body formation in a Cellular Model of huntington disease
2013Co-Authors: Kirill Bersuker, Mark S Hipp, Barbara Calamini, Richard I Morimoto, Ron R KopitoAbstract:The Cellular heat shock response (HSR) protects cells from toxicity associated with defective protein folding, and this pathway is widely viewed as a potential pharmacological target to treat neurodegenerative diseases linked to protein aggregation. Here we show that the HSR is not activated by mutant huntingtin (HTT) even in cells selected for the highest expression levels and for the presence of inclusion bodies containing aggregated protein. Surprisingly, HSR activation by HSF1 overexpression or by administration of a small molecule activator lowers the concentration threshold at which HTT forms inclusion bodies in cells expressing aggregation-prone, polyglutamine-expanded fragments of HTT. These data suggest that the HSR does not mitigate inclusion body formation.
Vittavat Termglinchan - One of the best experts on this subject based on the ideXlab platform.
-
abstract 20145 anemone toxin ii unmasks dilated cardiomyopathy phenotype in induced pluripotent stem cell derived cardiomyocyte Model
2017Co-Authors: Karim Sallam, Wu Haodi, Nazish Sayed, Junewha Rhee, Jared M Churko, Ian Y Chen, Alexa Wnorowski, Vittavat TermglinchanAbstract:Introduction: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have been used to as a Cellular Model of cardiac disorders including dilated cardiomyopathy (DCM) demonstrating excelle...
Frederic Frottin - One of the best experts on this subject based on the ideXlab platform.
-
multiple pathways of toxicity induced by c9orf72 dipeptide repeat aggregates and g4c2 rna in a Cellular Model
2021Co-Authors: Frederic Frottin, Manuela Perezberlanga, Ulrich F Hartl, Mark S HippAbstract:The most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia is a G4C2 repeat expansion in the C9orf72 gene. This expansion gives rise to translation of aggregating dipeptide repeat (DPR) proteins, including poly-GA as the most abundant species. However, gain of toxic function effects have been attributed to either the DPRs or the pathological G4C2 RNA. Here, we analyzed in a Cellular Model the relative toxicity of DPRs and RNA. Cytoplasmic poly-GA aggregates, generated in the absence of G4C2 RNA, interfered with nucleocytoplasmic protein transport, but had little effect on cell viability. In contrast, nuclear poly-GA was more toxic, impairing nucleolar protein quality control and protein biosynthesis. Production of the G4C2 RNA strongly reduced viability independent of DPR translation and caused pronounced inhibition of nuclear mRNA export and protein biogenesis. Thus, while the toxic effects of G4C2 RNA predominate in the Cellular Model used, DPRs exert additive effects that may contribute to pathology.
-
multiple pathways of toxicity induced by c9orf72 dipeptide repeat aggregates and g4c2 rna in a Cellular Model
2020Co-Authors: Frederic Frottin, Manuela Perezberlanga, Ulrich F Hartl, Mark S HippAbstract:Abstract The most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia is a G4C2 repeat expansion in the C9orf72 gene. This expansion gives rise to translation of aggregating dipeptide repeat (DPR) proteins, including poly-GA as the most abundant species. However, gain of toxic function effects have been attributed to either the DPRs or the pathological G4C2 RNA. Here we analyzed in a Cellular Model the relative toxicity of DPRs and RNA. Cytoplasmic poly-GA aggregates, generated in the absence of G4C2 RNA, interfered with nucleocytoplasmic protein transport, but had little effect on cell viability. In contrast, nuclear poly-GA was more toxic, impairing nucleolar protein quality control and protein biosynthesis. Production of the G4C2 RNA strongly reduced viability independent of DPR translation and caused pronounced inhibition of nuclear mRNA export and protein biogenesis. Thus, while the toxic effects of G4C2 RNA predominate, DPRs exert additive effects that may contribute to pathology.
Larisa Bobrovskaya - One of the best experts on this subject based on the ideXlab platform.
-
bioactive constituents from cinnamon hemp seed and polygonum cuspidatum protect against h2o2 but not rotenone toxicity in a Cellular Model of parkinson s disease
2018Co-Authors: Suzanne A Maiolo, Larisa BobrovskayaAbstract:Abstract Mitochondrial dysfunction and oxidative stress are two factors that are thought to contribute to the pathogenesis of Parkinson's disease (PD), a debilitating progressive neurodegenerative disorder that results in the loss of catecholamine producing cells throughout specific regions of the brain. In this study we aimed to compare the effects of hydrogen peroxide (H2O2) and rotenone (a pesticide and mitochondrial complex 1 inhibitor) on cell viability and the expression of tyrosine hydroxylase (TH) in a Cellular Model of PD. We also sought to investigate the potential neuroprotective benefits of bioactive constituents from cinnamon, hemp seed and polygonum cuspidatum. To create a Model, SH-SY5Y cells transfected with human TH isoform 1 were treated with varying concentrations of H2O2 and rotenone, in the presence or absence of bioactive constituents. The effect of these toxins and constituents on cell viability, apoptosis and protein expression was assessed using MTT viability assays and western blotting. Rotenone treatment caused a significant decrease in cell viability but a significant increase in TH in the remaining cells. H2O2 treatment caused a significant decrease in cell viability but had no significant effect on TH expression. Curcumin, cinnamaldehyde, caffeoyltyramide (hemp seed extract) and piceatannol glucoside (polygonum cuspidatum extract) were unable to attenuate rotenone induced cell death, however they were able to provide protection against H2O2 induced cell death. This is the first study to demonstrate the neuroprotective properties of cinnamaldehyde, caffeoyltyramide and piceatannol glucoside in a dopaminergic cell line in response to H2O2.
-
Bioactive constituents from cinnamon, hemp seed and polygonum cuspidatum protect against H2O2 but not rotenone toxicity in a Cellular Model of Parkinson's disease
2018Co-Authors: Suzanne A Maiolo, Peihong Fan, Larisa BobrovskayaAbstract:Mitochondrial dysfunction and oxidative stress are two factors that are thought to contribute to the pathogenesis of Parkinson's disease (PD), a debilitating progressive neurodegenerative disorder that results in the loss of catecholamine producing cells throughout specific regions of the brain. In this study we aimed to compare the effects of hydrogen peroxide (H2O2) and rotenone (a pesticide and mitochondrial complex 1 inhibitor) on cell viability and the expression of tyrosine hydroxylase (TH) in a Cellular Model of PD. We also sought to investigate the potential neuroprotective benefits of bioactive constituents from cinnamon, hemp seed and polygonum cuspidatum. To create a Model, SH-SY5Y cells transfected with human TH isoform 1 were treated with varying concentrations of H2O2 and rotenone, in the presence or absence of bioactive constituents. The effect of these toxins and constituents on cell viability, apoptosis and protein expression was assessed using MTT viability assays and western blotting. Rotenone treatment caused a significant decrease in cell viability but a significant increase in TH in the remaining cells. H2O2 treatment caused a significant decrease in cell viability but had no significant effect on TH expression. Curcumin, cinnamaldehyde, caffeoyltyramide (hemp seed extract) and piceatannol glucoside (polygonum cuspidatum extract) were unable to attenuate rotenone induced cell death, however they were able to provide protection against H2O2 induced cell death. This is the first study to demonstrate the neuroprotective properties of cinnamaldehyde, caffeoyltyramide and piceatannol glucoside in a dopaminergic cell line in response to H2O2. Keywords: Cinnamon, Hemp seed, Oxidative stress, Polygonum cuspidatum, Parkinson's disease, Rotenon
Karim Sallam - One of the best experts on this subject based on the ideXlab platform.
-
abstract 20145 anemone toxin ii unmasks dilated cardiomyopathy phenotype in induced pluripotent stem cell derived cardiomyocyte Model
2017Co-Authors: Karim Sallam, Wu Haodi, Nazish Sayed, Junewha Rhee, Jared M Churko, Ian Y Chen, Alexa Wnorowski, Vittavat TermglinchanAbstract:Introduction: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have been used to as a Cellular Model of cardiac disorders including dilated cardiomyopathy (DCM) demonstrating excelle...
