The growth factor glucagon-like peptide-1（GLP-1） is neuroprotective in several animal models of neurodegeneration. Here, we analyzed the neuroprotective effects of a novel protease-resistant GLP-1 analogue,（Val^8）...The growth factor glucagon-like peptide-1（GLP-1） is neuroprotective in several animal models of neurodegeneration. Here, we analyzed the neuroprotective effects of a novel protease-resistant GLP-1 analogue,（Val^8）GLP-1-Glu-PAL, which has advantages over older analogues, such as improvement of hippocampal neurogenesis, glucose homeostasis, and insulin secretion. We established an in vitro model of Parkinson＇s disease using the mitochondrial stressor rotenone in primary cultured mouse neurons pretreated with（Val^8）GLP-1-Glu-PAL.（Val^8）GLP-1-Glu-PAL alone did not affect neuronal viability, but prevented the rotenone-induced reduction in cell viability in a dose-dependent manner. In addition,（Val^8）GLP-1-Glu-PAL pretreatment prevented rotenone-induced proapoptotic changes manifesting as downregulation of procaspase-3 and Bcl-2 and upregulation of cleaved caspase-3. These results demonstrate that the novel agent（Val^8）GLP-1-GluPAL shows promise as a drug treatment for Parkinson＇s disease.展开更多
Geniposide, a monomer extracted from gardenia and widely used in Chinese medicine, is a novel agonist at the glucagon-like peptide-1 receptor. This receptor is involved in neuroprotection. In the present study, we sou...Geniposide, a monomer extracted from gardenia and widely used in Chinese medicine, is a novel agonist at the glucagon-like peptide-1 receptor. This receptor is involved in neuroprotection. In the present study, we sought to identify an anti-apoptotic mechanism for the treatment of neurodegenerative diseases. Primary cultured neurons were treated with different concentrations of rotenone for 48 hours. Morphological observation, cell counting kit-8 assay, lactate dehydrogenase detection and western blot assay demonstrated that 0.5 n M rotenone increased lactate dehydrogenase release, decreased the expression of procaspase-3 and Bcl-2, and increased cleaved caspase-3 expression in normal neurons. All these effects were prevented by geniposide. Our results indicate that geniposide diminished rotenone-induced injury in primary neurons by suppressing apoptosis. This may be one of the molecular mechanisms underlying the efficacy of geniposide in the treatment of neurodegenerative diseases.展开更多
基金supported by a grant from the Shanxi Science and Technology Department of China,No.2011081060a grant from Shanxi Scholarship Council of China,No.2011-44a grant from the Cure Parkinson’s Trust UK to CH
文摘The growth factor glucagon-like peptide-1（GLP-1） is neuroprotective in several animal models of neurodegeneration. Here, we analyzed the neuroprotective effects of a novel protease-resistant GLP-1 analogue,（Val^8）GLP-1-Glu-PAL, which has advantages over older analogues, such as improvement of hippocampal neurogenesis, glucose homeostasis, and insulin secretion. We established an in vitro model of Parkinson＇s disease using the mitochondrial stressor rotenone in primary cultured mouse neurons pretreated with（Val^8）GLP-1-Glu-PAL.（Val^8）GLP-1-Glu-PAL alone did not affect neuronal viability, but prevented the rotenone-induced reduction in cell viability in a dose-dependent manner. In addition,（Val^8）GLP-1-Glu-PAL pretreatment prevented rotenone-induced proapoptotic changes manifesting as downregulation of procaspase-3 and Bcl-2 and upregulation of cleaved caspase-3. These results demonstrate that the novel agent（Val^8）GLP-1-GluPAL shows promise as a drug treatment for Parkinson＇s disease.
基金supported by grants from the Shanxi Science and Technology Department in China,No.2011081060Shanxi Scholarship Council of China,No.2011-44
文摘Geniposide, a monomer extracted from gardenia and widely used in Chinese medicine, is a novel agonist at the glucagon-like peptide-1 receptor. This receptor is involved in neuroprotection. In the present study, we sought to identify an anti-apoptotic mechanism for the treatment of neurodegenerative diseases. Primary cultured neurons were treated with different concentrations of rotenone for 48 hours. Morphological observation, cell counting kit-8 assay, lactate dehydrogenase detection and western blot assay demonstrated that 0.5 n M rotenone increased lactate dehydrogenase release, decreased the expression of procaspase-3 and Bcl-2, and increased cleaved caspase-3 expression in normal neurons. All these effects were prevented by geniposide. Our results indicate that geniposide diminished rotenone-induced injury in primary neurons by suppressing apoptosis. This may be one of the molecular mechanisms underlying the efficacy of geniposide in the treatment of neurodegenerative diseases.
