User talk:Anders Lewisesquerre: Difference between revisions
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== Mechanism == | == Mechanism == | ||
Effects of the mammalian neurotrophin family of proteins are accomplished through activation of the tropomyosin-related kinase receptor family (TrkA, TrkB, and TrkC), and the p75 neurotrophin receptor, which is a member of the tumor necrosis factor receptor superfamily. Binding to the p75 neurotrophin receptor leads to neurite outgrowth via Trk modulation, and activation of <scene name='10/1078788/c-jun N-terminal kinase/1'>JNK</scene> (JNK), which leads to apoptosis. As a reference, the complex formed upon binding of Nerve growth factor (NGF) – a neurotrophin with close structural homology to BDNF – to the p75 receptor is <scene name='10/1078788/Ngf_and_p75_receptor/2'>shown</scene>, where NGF is shown in lime, and the p75 receptor is shown in fuchsia. BDNF binds to <scene name='10/1078788/Trkb_receptor/2'>tropomyosin receptor kinase B</scene> (TrkB), which results in activation of three different signaling cascades. These signaling pathways cause activation of CREB and CREB-binding protein (CBP), transcription factors which regulate expression of genes involved in neural plasticity, cell survival, and stress resistance. | Effects of the mammalian neurotrophin family of proteins are accomplished through activation of the tropomyosin-related kinase receptor family (TrkA, TrkB, and TrkC), and the p75 neurotrophin receptor, which is a member of the tumor necrosis factor receptor superfamily. Binding to the p75 neurotrophin receptor leads to neurite outgrowth via Trk modulation, and activation of <scene name='10/1078788/c-jun N-terminal kinase/1'>JNK</scene> (JNK), which leads to apoptosis. As a reference, the complex formed upon binding of Nerve growth factor (NGF) – a neurotrophin with close structural homology to BDNF – to the p75 receptor is <scene name='10/1078788/Ngf_and_p75_receptor/2'>shown</scene>, where NGF is shown in lime, and the p75 receptor is shown in fuchsia. BDNF binds to <scene name='10/1078788/Trkb_receptor/2'>tropomyosin receptor kinase B</scene> (TrkB), which results in activation of three different signaling cascades. These signaling pathways cause activation of CREB and CREB-binding protein (CBP), transcription factors which regulate expression of genes involved in neural plasticity, cell survival, and stress resistance. | ||
'''IRS-1/PI3K/AKT pathway''' | The '''IRS-1/PI3K/AKT pathway''' | ||
Involves sequential activation of Insulin receptor substrate 1 (IRS1/2), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (Akt). The pathway activates protein kinase A (Akt) which suppresses apoptosis | Involves sequential activation of Insulin receptor substrate 1 (IRS1/2), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (Akt). The pathway activates protein kinase A (Akt) which suppresses apoptosis | ||
'''Ras/MAPK/ERK pathway''' | In the '''Ras/MAPK/ERK pathway''', | ||
Ras activates the Ras/MAPK/ERK pathway, as well as the PIK3, and PLC pathways. MAPK/ERK promotes cell survival by induction of pro survival genes and inhibition of pro-apoptotic proteins | Ras activates the Ras/MAPK/ERK pathway, as well as the PIK3, and PLC pathways. MAPK/ERK promotes cell survival by induction of pro survival genes and inhibition of pro-apoptotic proteins | ||
'''PLC/DAG/IP3 pathway''' | The third cascade is the '''PLC/DAG/IP3 pathway''', where | ||
PLC-𝛾 is phosphorylated by BDNF binding to the TrkB receptor, leading to production of IP3 and DAG. IP3 increases intracellular calcium concentrations, and DAG regulates protein kinase C, which is important in the MAPK/ERK pathway. | PLC-𝛾 is phosphorylated by BDNF binding to the TrkB receptor, leading to production of IP3 and DAG. IP3 increases intracellular calcium concentrations, and DAG regulates protein kinase C, which is important in the MAPK/ERK pathway. | ||
