gambogic-acid and Cerebral-Infarction

gambogic-acid has been researched along with Cerebral-Infarction* in 1 studies

Other Studies

1 other study(ies) available for gambogic-acid and Cerebral-Infarction

Article	Year
Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death. Proceedings of the National Academy of Sciences of the United States of America, 2007, Oct-09, Volume: 104, Issue:41 Nerve growth factor (NGF) binds to TrkA receptor and triggers activation of numerous signaling cascades, which play critical roles in neuronal plasticity, survival, and neurite outgrowth. To mimic NGF functions pharmacologically, we developed a high-throughput screening assay to identify small-molecule agonists for TrkA receptor. The most potent compound, gambogic amide, selectively binds to TrkA, but not TrkB or TrkC, and robustly induces its tyrosine phosphorylation and downstream signaling activation, including Akt and MAPKs. Further, it strongly prevents glutamate-induced neuronal cell death and provokes prominent neurite outgrowth in PC12 cells. Gambogic amide specifically interacts with the cytoplasmic juxtamembrane domain of TrkA receptor and triggers its dimerization. Administration of this molecule in mice substantially diminishes kainic acid-triggered neuronal cell death and decreases infarct volume in the transient middle cerebral artery occlusion model of stroke. Thus, gambogic amide might not only establish a powerful platform for dissection of the physiological roles of NGF and TrkA receptor but also provide effective treatments for neurodegenerative diseases and stroke. Topics: Amides; Animals; Apoptosis; Cell Line; Cerebral Infarction; Hippocampus; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Nerve Growth Factors; Neurites; Neurons; PC12 Cells; Proto-Oncogene Proteins c-akt; Rats; Receptor, trkA; Xanthones	2007

Article

Year

Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death.

Proceedings of the National Academy of Sciences of the United States of America, 2007, Oct-09, Volume: 104, Issue:41

Nerve growth factor (NGF) binds to TrkA receptor and triggers activation of numerous signaling cascades, which play critical roles in neuronal plasticity, survival, and neurite outgrowth. To mimic NGF functions pharmacologically, we developed a high-throughput screening assay to identify small-molecule agonists for TrkA receptor. The most potent compound, gambogic amide, selectively binds to TrkA, but not TrkB or TrkC, and robustly induces its tyrosine phosphorylation and downstream signaling activation, including Akt and MAPKs. Further, it strongly prevents glutamate-induced neuronal cell death and provokes prominent neurite outgrowth in PC12 cells. Gambogic amide specifically interacts with the cytoplasmic juxtamembrane domain of TrkA receptor and triggers its dimerization. Administration of this molecule in mice substantially diminishes kainic acid-triggered neuronal cell death and decreases infarct volume in the transient middle cerebral artery occlusion model of stroke. Thus, gambogic amide might not only establish a powerful platform for dissection of the physiological roles of NGF and TrkA receptor but also provide effective treatments for neurodegenerative diseases and stroke.

Topics: Amides; Animals; Apoptosis; Cell Line; Cerebral Infarction; Hippocampus; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Nerve Growth Factors; Neurites; Neurons; PC12 Cells; Proto-Oncogene Proteins c-akt; Rats; Receptor, trkA; Xanthones

2007