The Experts below are selected from a list of 3 Experts worldwide ranked by ideXlab platform
Franziska Richter - One of the best experts on this subject based on the ideXlab platform.
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A GCase Chaperone Improves Motor Function in a Mouse Model of Synucleinopathy
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2014Co-Authors: Franziska Richter, Sheila M. Fleming, Melanie B. Watson, Vincent Lemesre, Lee Pellegrino, Brian Ranes, Chunni Zhu, Farzad Mortazavi, Caitlin K. Mulligan, Pedrom C. SioshansiAbstract:Mutation of the lysosomal hydrolase acid-β-glucosidase (GCase), which leads to reduced GCase activity, is one of the most frequent genetic risk factors for Parkinson’s disease (PD) and promotes α-synuclein accumulation in the brain, a hallmark of PD and other synucleinopathies. Whether targeting GCase pharmacologically is a valid therapeutic strategy for sporadic PD in the absence of GCase mutation is unknown. We have investigated whether increasing the stability, trafficking, and activity of wild-type GCase could be beneficial in synucleinopathies by administering the pharmacological chaperone AT2101 (Afegostat-tartrate, isofagomine) to mice that overexpress human wild-type α-synuclein (Thy1-aSyn mice). AT2101 administered orally for 4 months to Thy1-aSyn mice improved motor and nonmotor function, abolished microglial inflammatory response in the substantia nigra, reduced α-synuclein immunoreactivity in nigral dopaminergic neurons, and reduced the number of small α-synuclein aggregates, while increasing the number of large α-synuclein aggregates. These data support the further investigation of pharmacological chaperones that target GCase as a therapeutic approach for sporadic PD and other synucleinopathies, even in the absence of glucocerebrosidase mutations.
Sheila M. Fleming - One of the best experts on this subject based on the ideXlab platform.
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A GCase Chaperone Improves Motor Function in a Mouse Model of Synucleinopathy
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2014Co-Authors: Franziska Richter, Sheila M. Fleming, Melanie B. Watson, Vincent Lemesre, Lee Pellegrino, Brian Ranes, Chunni Zhu, Farzad Mortazavi, Caitlin K. Mulligan, Pedrom C. SioshansiAbstract:Mutation of the lysosomal hydrolase acid-β-glucosidase (GCase), which leads to reduced GCase activity, is one of the most frequent genetic risk factors for Parkinson’s disease (PD) and promotes α-synuclein accumulation in the brain, a hallmark of PD and other synucleinopathies. Whether targeting GCase pharmacologically is a valid therapeutic strategy for sporadic PD in the absence of GCase mutation is unknown. We have investigated whether increasing the stability, trafficking, and activity of wild-type GCase could be beneficial in synucleinopathies by administering the pharmacological chaperone AT2101 (Afegostat-tartrate, isofagomine) to mice that overexpress human wild-type α-synuclein (Thy1-aSyn mice). AT2101 administered orally for 4 months to Thy1-aSyn mice improved motor and nonmotor function, abolished microglial inflammatory response in the substantia nigra, reduced α-synuclein immunoreactivity in nigral dopaminergic neurons, and reduced the number of small α-synuclein aggregates, while increasing the number of large α-synuclein aggregates. These data support the further investigation of pharmacological chaperones that target GCase as a therapeutic approach for sporadic PD and other synucleinopathies, even in the absence of glucocerebrosidase mutations.
Melanie B. Watson - One of the best experts on this subject based on the ideXlab platform.
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A GCase Chaperone Improves Motor Function in a Mouse Model of Synucleinopathy
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2014Co-Authors: Franziska Richter, Sheila M. Fleming, Melanie B. Watson, Vincent Lemesre, Lee Pellegrino, Brian Ranes, Chunni Zhu, Farzad Mortazavi, Caitlin K. Mulligan, Pedrom C. SioshansiAbstract:Mutation of the lysosomal hydrolase acid-β-glucosidase (GCase), which leads to reduced GCase activity, is one of the most frequent genetic risk factors for Parkinson’s disease (PD) and promotes α-synuclein accumulation in the brain, a hallmark of PD and other synucleinopathies. Whether targeting GCase pharmacologically is a valid therapeutic strategy for sporadic PD in the absence of GCase mutation is unknown. We have investigated whether increasing the stability, trafficking, and activity of wild-type GCase could be beneficial in synucleinopathies by administering the pharmacological chaperone AT2101 (Afegostat-tartrate, isofagomine) to mice that overexpress human wild-type α-synuclein (Thy1-aSyn mice). AT2101 administered orally for 4 months to Thy1-aSyn mice improved motor and nonmotor function, abolished microglial inflammatory response in the substantia nigra, reduced α-synuclein immunoreactivity in nigral dopaminergic neurons, and reduced the number of small α-synuclein aggregates, while increasing the number of large α-synuclein aggregates. These data support the further investigation of pharmacological chaperones that target GCase as a therapeutic approach for sporadic PD and other synucleinopathies, even in the absence of glucocerebrosidase mutations.
Vincent Lemesre - One of the best experts on this subject based on the ideXlab platform.
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A GCase Chaperone Improves Motor Function in a Mouse Model of Synucleinopathy
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2014Co-Authors: Franziska Richter, Sheila M. Fleming, Melanie B. Watson, Vincent Lemesre, Lee Pellegrino, Brian Ranes, Chunni Zhu, Farzad Mortazavi, Caitlin K. Mulligan, Pedrom C. SioshansiAbstract:Mutation of the lysosomal hydrolase acid-β-glucosidase (GCase), which leads to reduced GCase activity, is one of the most frequent genetic risk factors for Parkinson’s disease (PD) and promotes α-synuclein accumulation in the brain, a hallmark of PD and other synucleinopathies. Whether targeting GCase pharmacologically is a valid therapeutic strategy for sporadic PD in the absence of GCase mutation is unknown. We have investigated whether increasing the stability, trafficking, and activity of wild-type GCase could be beneficial in synucleinopathies by administering the pharmacological chaperone AT2101 (Afegostat-tartrate, isofagomine) to mice that overexpress human wild-type α-synuclein (Thy1-aSyn mice). AT2101 administered orally for 4 months to Thy1-aSyn mice improved motor and nonmotor function, abolished microglial inflammatory response in the substantia nigra, reduced α-synuclein immunoreactivity in nigral dopaminergic neurons, and reduced the number of small α-synuclein aggregates, while increasing the number of large α-synuclein aggregates. These data support the further investigation of pharmacological chaperones that target GCase as a therapeutic approach for sporadic PD and other synucleinopathies, even in the absence of glucocerebrosidase mutations.
Lee Pellegrino - One of the best experts on this subject based on the ideXlab platform.
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A GCase Chaperone Improves Motor Function in a Mouse Model of Synucleinopathy
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2014Co-Authors: Franziska Richter, Sheila M. Fleming, Melanie B. Watson, Vincent Lemesre, Lee Pellegrino, Brian Ranes, Chunni Zhu, Farzad Mortazavi, Caitlin K. Mulligan, Pedrom C. SioshansiAbstract:Mutation of the lysosomal hydrolase acid-β-glucosidase (GCase), which leads to reduced GCase activity, is one of the most frequent genetic risk factors for Parkinson’s disease (PD) and promotes α-synuclein accumulation in the brain, a hallmark of PD and other synucleinopathies. Whether targeting GCase pharmacologically is a valid therapeutic strategy for sporadic PD in the absence of GCase mutation is unknown. We have investigated whether increasing the stability, trafficking, and activity of wild-type GCase could be beneficial in synucleinopathies by administering the pharmacological chaperone AT2101 (Afegostat-tartrate, isofagomine) to mice that overexpress human wild-type α-synuclein (Thy1-aSyn mice). AT2101 administered orally for 4 months to Thy1-aSyn mice improved motor and nonmotor function, abolished microglial inflammatory response in the substantia nigra, reduced α-synuclein immunoreactivity in nigral dopaminergic neurons, and reduced the number of small α-synuclein aggregates, while increasing the number of large α-synuclein aggregates. These data support the further investigation of pharmacological chaperones that target GCase as a therapeutic approach for sporadic PD and other synucleinopathies, even in the absence of glucocerebrosidase mutations.