The Experts below are selected from a list of 1743 Experts worldwide ranked by ideXlab platform
Manabu Nakashima - One of the best experts on this subject based on the ideXlab platform.
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a chemical chaperone sodium 4 Phenylbutyric Acid attenuates the pathogenic potency in human α synuclein a30p a53t transgenic mice
Parkinsonism & Related Disorders, 2009Co-Authors: Kazuhiko Ono, Miyuki Ikemoto, Takeshi Kawarabayashi, Masaki Ikeda, Takuya Nishinakagawa, Masato Hosokawa, Mikio Shoji, Mitsuo Takahashi, Manabu NakashimaAbstract:Aggregation and cytotoxicity of misfolded alpha-synuclein are postulated to be crucial in the disease processes of Parkinson's disease (PD) and other synucleinopathies. Mutations in the alpha-synuclein gene in some pedigrees of familial PD have been reported. The mutant alpha-synuclein has been reported to form fibrillar aggregates resulting in biochemical abnormalities that are responsible for the onset of familial PD. Thus, any agent that effectively prevents the development of misfolded and aggregated alpha-synuclein would be a disease modifying therapeutic candidate. We examined the efficacy of sodium 4-Phenylbutyric Acid (PBA), one of the chemical chaperons, in transgenic (Tg) mice overexpressing human alpha-synuclein containing a double mutation (A30P + A53T). To evaluate the therapeutic efficacy, bradykinesia and motor coordination were assessed using a pole test and a rotarod treadmill task, respectively. After PBA treatment, these motor deteriorations gradually improved. In immunohistochemical examinations, both a loss of tyrosine hydroxylase-positive neurons and an increase of phosphorylated alpha-synuclein in the substantia nigra were inhibited, resulting in no depletion of the striatal dopamine content. These data suggest that PBA might be one of the therapeutic reagents for neurodegenerative disorders.
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A chemical chaperone, sodium 4-Phenylbutyric Acid, attenuates the pathogenic potency in human α-synuclein A30P + A53T transgenic mice
Parkinsonism & related disorders, 2009Co-Authors: Kazuhiko Ono, Miyuki Ikemoto, Takeshi Kawarabayashi, Masaki Ikeda, Takuya Nishinakagawa, Masato Hosokawa, Mikio Shoji, Mitsuo Takahashi, Manabu NakashimaAbstract:Abstract Aggregation and cytotoxicity of misfolded α-synuclein are postulated to be crucial in the disease processes of Parkinson's disease (PD) and other synucleinopathies. Mutations in the α-synuclein gene in some pedigrees of familial PD have been reported. The mutant α-synuclein has been reported to form fibrillar aggregates resulting in biochemical abnormalities that are responsible for the onset of familial PD. Thus, any agent that effectively prevents the development of misfolded and aggregated α-synuclein would be a disease modifying therapeutic candidate. We examined the efficacy of sodium 4-Phenylbutyric Acid (PBA), one of the chemical chaperons, in transgenic (Tg) mice overexpressing human α-synuclein containing a double mutation (A30P + A53T). To evaluate the therapeutic efficacy, bradykinesia and motor coordination were assessed using a pole test and a rotarod treadmill task, respectively. After PBA treatment, these motor deteriorations gradually improved. In immunohistochemical examinations, both a loss of tyrosine hydroxylase-positive neurons and an increase of phosphorylated α-synuclein in the substantia nigra were inhibited, resulting in no depletion of the striatal dopamine content. These data suggest that PBA might be one of the therapeutic reagents for neurodegenerative disorders.
Kazuhiko Ono - One of the best experts on this subject based on the ideXlab platform.
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a chemical chaperone sodium 4 Phenylbutyric Acid attenuates the pathogenic potency in human α synuclein a30p a53t transgenic mice
Parkinsonism & Related Disorders, 2009Co-Authors: Kazuhiko Ono, Miyuki Ikemoto, Takeshi Kawarabayashi, Masaki Ikeda, Takuya Nishinakagawa, Masato Hosokawa, Mikio Shoji, Mitsuo Takahashi, Manabu NakashimaAbstract:Aggregation and cytotoxicity of misfolded alpha-synuclein are postulated to be crucial in the disease processes of Parkinson's disease (PD) and other synucleinopathies. Mutations in the alpha-synuclein gene in some pedigrees of familial PD have been reported. The mutant alpha-synuclein has been reported to form fibrillar aggregates resulting in biochemical abnormalities that are responsible for the onset of familial PD. Thus, any agent that effectively prevents the development of misfolded and aggregated alpha-synuclein would be a disease modifying therapeutic candidate. We examined the efficacy of sodium 4-Phenylbutyric Acid (PBA), one of the chemical chaperons, in transgenic (Tg) mice overexpressing human alpha-synuclein containing a double mutation (A30P + A53T). To evaluate the therapeutic efficacy, bradykinesia and motor coordination were assessed using a pole test and a rotarod treadmill task, respectively. After PBA treatment, these motor deteriorations gradually improved. In immunohistochemical examinations, both a loss of tyrosine hydroxylase-positive neurons and an increase of phosphorylated alpha-synuclein in the substantia nigra were inhibited, resulting in no depletion of the striatal dopamine content. These data suggest that PBA might be one of the therapeutic reagents for neurodegenerative disorders.
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A chemical chaperone, sodium 4-Phenylbutyric Acid, attenuates the pathogenic potency in human α-synuclein A30P + A53T transgenic mice
Parkinsonism & related disorders, 2009Co-Authors: Kazuhiko Ono, Miyuki Ikemoto, Takeshi Kawarabayashi, Masaki Ikeda, Takuya Nishinakagawa, Masato Hosokawa, Mikio Shoji, Mitsuo Takahashi, Manabu NakashimaAbstract:Abstract Aggregation and cytotoxicity of misfolded α-synuclein are postulated to be crucial in the disease processes of Parkinson's disease (PD) and other synucleinopathies. Mutations in the α-synuclein gene in some pedigrees of familial PD have been reported. The mutant α-synuclein has been reported to form fibrillar aggregates resulting in biochemical abnormalities that are responsible for the onset of familial PD. Thus, any agent that effectively prevents the development of misfolded and aggregated α-synuclein would be a disease modifying therapeutic candidate. We examined the efficacy of sodium 4-Phenylbutyric Acid (PBA), one of the chemical chaperons, in transgenic (Tg) mice overexpressing human α-synuclein containing a double mutation (A30P + A53T). To evaluate the therapeutic efficacy, bradykinesia and motor coordination were assessed using a pole test and a rotarod treadmill task, respectively. After PBA treatment, these motor deteriorations gradually improved. In immunohistochemical examinations, both a loss of tyrosine hydroxylase-positive neurons and an increase of phosphorylated α-synuclein in the substantia nigra were inhibited, resulting in no depletion of the striatal dopamine content. These data suggest that PBA might be one of the therapeutic reagents for neurodegenerative disorders.
Weixing Wang - One of the best experts on this subject based on the ideXlab platform.
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effects of 4 Phenylbutyric Acid on severe acute pancreatitis induced liver injury in rats by inositol requiring enzyme 1α signaling pathway
Chinese journal of experimental surgery, 2019Co-Authors: Qiang Yin, Weixing Wang, Yu-pu HongAbstract:Objective To explore the effects of 4-Phenylbutyric Acid (PBA) on severe acute pancreatitis (SAP)-induced liver injury in rats by inositol requiring enzyme-1α (IRE1α) signaling pathway. Methods Thirty-six SD rats were randomly divided into three groups (n=12): shame operation (SO) group, SAP group and 4-Phenylbutyric Acid (PBA) group. All rats were sacrificed at 12 h after the SAP model to measure the serum levels of anylase (AMY), alanine aminotransferase (ALT), glutamic oxalacetic transaminase (AST) and the contents of tumor necrosis factor-α (TNF-α). Liver was collected to exam the pathological changes, the apoptosis and the expression of GRP78, IRE1α, nuclear factor-κB (NF-κB) p65, inhibitor of NF-κB (IκB), phosphorylated c-Jun N-terminal kinase (p-JNK), bcl-2, cysteinyl aspartate-specific protease (Caspase)-3. Results Compared with SO group, the serum levels of AMY [(5 570.6±564.2) vs. (871.6±222.5)], ALT [(130.3±23.1) vs. (42.4±12.3)] and AST [(462.9±63.3) vs. (166.5±41.8)], as well as the expression of TNF-α [(264.8±30.9) vs. (118.6±30.3)] were raised (P<0.05); the degree of hepatic necrosis and apoptosis was higher; the expression of GRP78, IRE1α, p-JNK, NF-κB p65, Caspase-3 [(0.73±0.07) vs. (0.55±0.03), (0.79±0.08) vs. (0.57±0.04), (0.58±0.04) vs. (0.33±0.01), (0.59±0.05) vs. (0.45±0.02), (0.80±0.06) vs. (0.51±0.03)] was increased and the expression of IκB and bcl-2 [(0.36±0.03) vs. (0.47±0.02), (0.52±0.04) vs. (0.73±0.03)] was decreased in SAP group (P<0.05). Compared with SAP group, the serum levels of AMY [(4 816.9±797.8) vs. (5 570.6±564.2)], ALT [(93.3±11.2) vs. (130.3±23.1)] and AST [(232.8±28.6) vs. (462.9±63.3)], as well as the expression of TNF-α [(186.7±25.1) vs. (264.8±30.9)] were reduced (P<0.05); the degree of hepatic necrosis and apoptosis was lower; the expression of GRP78, IRE1α, p-JNK, NF-κB p65, Caspase-3 [(0.65±0.05) vs. (0.73±0.07), (0.63±0.03) vs. (0.79±0.08), (0.46±0.03) vs. (0.58±0.04), (0.52±0.04) vs. (0.59±0.05), (0.66±0.05) vs. (0.80±0.06)] was decreased and the expression of IκB and bcl-2 [(0.42±0.04) vs. (0.36±0.03), (0.61±0.02) vs. (0.52±0.04)] was increased in PBA group (P<0.05). Conclusion PBA may reduce inflammation and apoptosis by inhibiting the IRE1α signaling pathway to protect severe acute pancreatitis-induced liver injury in rats. Key words: 4-Phenylbutyric Acid; Endoplasmic reticulum stress; Severe acute pancreatitis; Apoptosis; Inflammation
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Effects of 4-Phenylbutyric Acid on severe acute pancreatitis-induced liver injury in rats by inositol requiring enzyme-1α signaling pathway
Chinese journal of experimental surgery, 2019Co-Authors: Qiang Yin, Weixing Wang, Yu-pu HongAbstract:Objective To explore the effects of 4-Phenylbutyric Acid (PBA) on severe acute pancreatitis (SAP)-induced liver injury in rats by inositol requiring enzyme-1α (IRE1α) signaling pathway. Methods Thirty-six SD rats were randomly divided into three groups (n=12): shame operation (SO) group, SAP group and 4-Phenylbutyric Acid (PBA) group. All rats were sacrificed at 12 h after the SAP model to measure the serum levels of anylase (AMY), alanine aminotransferase (ALT), glutamic oxalacetic transaminase (AST) and the contents of tumor necrosis factor-α (TNF-α). Liver was collected to exam the pathological changes, the apoptosis and the expression of GRP78, IRE1α, nuclear factor-κB (NF-κB) p65, inhibitor of NF-κB (IκB), phosphorylated c-Jun N-terminal kinase (p-JNK), bcl-2, cysteinyl aspartate-specific protease (Caspase)-3. Results Compared with SO group, the serum levels of AMY [(5 570.6±564.2) vs. (871.6±222.5)], ALT [(130.3±23.1) vs. (42.4±12.3)] and AST [(462.9±63.3) vs. (166.5±41.8)], as well as the expression of TNF-α [(264.8±30.9) vs. (118.6±30.3)] were raised (P
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4-Phenylbutyric Acid Attenuates Endoplasmic Reticulum Stress-Mediated Intestinal Epithelial Cell Apoptosis in Rats with Severe Acute Pancreatitis.
Digestive diseases and sciences, 2019Co-Authors: Yun-dong You, Wen-hong Deng, Wen-yi Guo, Liang Zhao, Fangchao Mei, Yu-pu Hong, Yu Zhou, Weixing WangAbstract:Objectives The present study aimed to determine whether intestinal epithelial cell (IECs) apoptosis could be induced by endoplasmic reticulum stress (ERS) in severe acute pancreatitis (SAP), and the role of chemical chaperone 4-Phenylbutyric Acid (4-PBA) in SAP-associated intestinal barrier injury.
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4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis.
International journal of endocrinology, 2016Co-Authors: Yu-pu Hong, Wen-yi Guo, Liang Zhao, Fangchao Mei, Weixing Wang, Mingwei Xiang, Ablikim Abliz, Wen-hong DengAbstract:Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-Phenylbutyric Acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment.
Takuya Nishinakagawa - One of the best experts on this subject based on the ideXlab platform.
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a chemical chaperone sodium 4 Phenylbutyric Acid attenuates the pathogenic potency in human α synuclein a30p a53t transgenic mice
Parkinsonism & Related Disorders, 2009Co-Authors: Kazuhiko Ono, Miyuki Ikemoto, Takeshi Kawarabayashi, Masaki Ikeda, Takuya Nishinakagawa, Masato Hosokawa, Mikio Shoji, Mitsuo Takahashi, Manabu NakashimaAbstract:Aggregation and cytotoxicity of misfolded alpha-synuclein are postulated to be crucial in the disease processes of Parkinson's disease (PD) and other synucleinopathies. Mutations in the alpha-synuclein gene in some pedigrees of familial PD have been reported. The mutant alpha-synuclein has been reported to form fibrillar aggregates resulting in biochemical abnormalities that are responsible for the onset of familial PD. Thus, any agent that effectively prevents the development of misfolded and aggregated alpha-synuclein would be a disease modifying therapeutic candidate. We examined the efficacy of sodium 4-Phenylbutyric Acid (PBA), one of the chemical chaperons, in transgenic (Tg) mice overexpressing human alpha-synuclein containing a double mutation (A30P + A53T). To evaluate the therapeutic efficacy, bradykinesia and motor coordination were assessed using a pole test and a rotarod treadmill task, respectively. After PBA treatment, these motor deteriorations gradually improved. In immunohistochemical examinations, both a loss of tyrosine hydroxylase-positive neurons and an increase of phosphorylated alpha-synuclein in the substantia nigra were inhibited, resulting in no depletion of the striatal dopamine content. These data suggest that PBA might be one of the therapeutic reagents for neurodegenerative disorders.
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A chemical chaperone, sodium 4-Phenylbutyric Acid, attenuates the pathogenic potency in human α-synuclein A30P + A53T transgenic mice
Parkinsonism & related disorders, 2009Co-Authors: Kazuhiko Ono, Miyuki Ikemoto, Takeshi Kawarabayashi, Masaki Ikeda, Takuya Nishinakagawa, Masato Hosokawa, Mikio Shoji, Mitsuo Takahashi, Manabu NakashimaAbstract:Abstract Aggregation and cytotoxicity of misfolded α-synuclein are postulated to be crucial in the disease processes of Parkinson's disease (PD) and other synucleinopathies. Mutations in the α-synuclein gene in some pedigrees of familial PD have been reported. The mutant α-synuclein has been reported to form fibrillar aggregates resulting in biochemical abnormalities that are responsible for the onset of familial PD. Thus, any agent that effectively prevents the development of misfolded and aggregated α-synuclein would be a disease modifying therapeutic candidate. We examined the efficacy of sodium 4-Phenylbutyric Acid (PBA), one of the chemical chaperons, in transgenic (Tg) mice overexpressing human α-synuclein containing a double mutation (A30P + A53T). To evaluate the therapeutic efficacy, bradykinesia and motor coordination were assessed using a pole test and a rotarod treadmill task, respectively. After PBA treatment, these motor deteriorations gradually improved. In immunohistochemical examinations, both a loss of tyrosine hydroxylase-positive neurons and an increase of phosphorylated α-synuclein in the substantia nigra were inhibited, resulting in no depletion of the striatal dopamine content. These data suggest that PBA might be one of the therapeutic reagents for neurodegenerative disorders.
Miyuki Ikemoto - One of the best experts on this subject based on the ideXlab platform.
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a chemical chaperone sodium 4 Phenylbutyric Acid attenuates the pathogenic potency in human α synuclein a30p a53t transgenic mice
Parkinsonism & Related Disorders, 2009Co-Authors: Kazuhiko Ono, Miyuki Ikemoto, Takeshi Kawarabayashi, Masaki Ikeda, Takuya Nishinakagawa, Masato Hosokawa, Mikio Shoji, Mitsuo Takahashi, Manabu NakashimaAbstract:Aggregation and cytotoxicity of misfolded alpha-synuclein are postulated to be crucial in the disease processes of Parkinson's disease (PD) and other synucleinopathies. Mutations in the alpha-synuclein gene in some pedigrees of familial PD have been reported. The mutant alpha-synuclein has been reported to form fibrillar aggregates resulting in biochemical abnormalities that are responsible for the onset of familial PD. Thus, any agent that effectively prevents the development of misfolded and aggregated alpha-synuclein would be a disease modifying therapeutic candidate. We examined the efficacy of sodium 4-Phenylbutyric Acid (PBA), one of the chemical chaperons, in transgenic (Tg) mice overexpressing human alpha-synuclein containing a double mutation (A30P + A53T). To evaluate the therapeutic efficacy, bradykinesia and motor coordination were assessed using a pole test and a rotarod treadmill task, respectively. After PBA treatment, these motor deteriorations gradually improved. In immunohistochemical examinations, both a loss of tyrosine hydroxylase-positive neurons and an increase of phosphorylated alpha-synuclein in the substantia nigra were inhibited, resulting in no depletion of the striatal dopamine content. These data suggest that PBA might be one of the therapeutic reagents for neurodegenerative disorders.
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A chemical chaperone, sodium 4-Phenylbutyric Acid, attenuates the pathogenic potency in human α-synuclein A30P + A53T transgenic mice
Parkinsonism & related disorders, 2009Co-Authors: Kazuhiko Ono, Miyuki Ikemoto, Takeshi Kawarabayashi, Masaki Ikeda, Takuya Nishinakagawa, Masato Hosokawa, Mikio Shoji, Mitsuo Takahashi, Manabu NakashimaAbstract:Abstract Aggregation and cytotoxicity of misfolded α-synuclein are postulated to be crucial in the disease processes of Parkinson's disease (PD) and other synucleinopathies. Mutations in the α-synuclein gene in some pedigrees of familial PD have been reported. The mutant α-synuclein has been reported to form fibrillar aggregates resulting in biochemical abnormalities that are responsible for the onset of familial PD. Thus, any agent that effectively prevents the development of misfolded and aggregated α-synuclein would be a disease modifying therapeutic candidate. We examined the efficacy of sodium 4-Phenylbutyric Acid (PBA), one of the chemical chaperons, in transgenic (Tg) mice overexpressing human α-synuclein containing a double mutation (A30P + A53T). To evaluate the therapeutic efficacy, bradykinesia and motor coordination were assessed using a pole test and a rotarod treadmill task, respectively. After PBA treatment, these motor deteriorations gradually improved. In immunohistochemical examinations, both a loss of tyrosine hydroxylase-positive neurons and an increase of phosphorylated α-synuclein in the substantia nigra were inhibited, resulting in no depletion of the striatal dopamine content. These data suggest that PBA might be one of the therapeutic reagents for neurodegenerative disorders.
