bp(GO:"GO:0031175")

Entity

Name

GO:0031175

Namespace

go

Namespace Version

20180828

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/1b20f0637c395f8aa89c2e2e342d7b704062c242/external/go.belns

Gambogic amide binds selectively to TrkA (but not TrkB or TrkC), phosphorylates TrkA tyrosine residues, and activates the Akt and MAPK TrkA-mediated NGF signaling pathways. Gambogic amide has been demonstrated to ameliorate excitotoxic damage and promote neurite outgrowth in PC12 cells [116], making this a potential lead compound for chemical modification and clinical trial assessment. PubMed:18986241

In this regard, immunoblotting studies demonstrated that proNGF is the predominant form of NGF present in the cortex of aged cognitively intact humans [60]. ProNGF levels are increased in the cortex of subjects diagnosed with MCI or mild AD compared to those with NCI [61]. The biological consequences of proNGF are controversial, as is the function of its accumulation in the cortex during the prodromal stages of AD. Emerging literature suggests that recombinant proNGF binds TrkA and promotes neuronal survival and neurite outgrowth similar to mature NGF, but is approximately fivefold less active than the mature NGF peptide [62,63]. PubMed:18986241

In this regard, immunoblotting studies demonstrated that proNGF is the predominant form of NGF present in the cortex of aged cognitively intact humans [60]. ProNGF levels are increased in the cortex of subjects diagnosed with MCI or mild AD compared to those with NCI [61]. The biological consequences of proNGF are controversial, as is the function of its accumulation in the cortex during the prodromal stages of AD. Emerging literature suggests that recombinant proNGF binds TrkA and promotes neuronal survival and neurite outgrowth similar to mature NGF, but is approximately fivefold less active than the mature NGF peptide [62,63]. PubMed:18986241

The classic MAPK cascade involves activation of the small GTPase Ras, and the kinases Raf and MEK [86,87]. Downstream consequences of MAPK activation include activation of the ribosomal S6 kinases (Rsk) and the MAPK-activated protein kinase 2 (MAPKAP2), which phosphorylates several transcription factors including Elk-1 and cAMP-regulated response element binding protein (CREB) [85]. The physiological significance of this elaborate NGF-induced network remains unclear, but the sustained activation of MAPK is linked to neurotrophin-mediated neurite outgrowth [88,89] PubMed:18986241

The classic MAPK cascade involves activation of the small GTPase Ras, and the kinases Raf and MEK [86,87]. Downstream consequences of MAPK activation include activation of the ribosomal S6 kinases (Rsk) and the MAPK-activated protein kinase 2 (MAPKAP2), which phosphorylates several transcription factors including Elk-1 and cAMP-regulated response element binding protein (CREB) [85]. The physiological significance of this elaborate NGF-induced network remains unclear, but the sustained activation of MAPK is linked to neurotrophin-mediated neurite outgrowth [88,89] PubMed:18986241