bp(HBP:Excitotoxicity)

Entity

Name

Excitotoxicity

Namespace

HBP

Namespace Version

20181029

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/785431732a26d6809b4162d98b95687d16404e63/export/hbp-names.belns

Nicotinic neuroprotection against non-Abeta toxicity is also mediated largely through alpha7 nAChRs. alpha7 nAChRs protect PC12 cells against ethanol toxicity (Li et al., 1999a) and from cell death associated with serum depletion (Ren et al., 2005); they protect cultured neurons against glutamate-induced excitotoxicity (Kaneko et al., 1997) and hippocampal slices against oxygen and glucose deprivation (Egea et al., 2007) through the activation of alpha7 nAChRs (Rosa et al., 2006). PubMed:19293145

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

Excitotoxicity leading to elevated intracellular calcium is a common feature of neurodegenerative diseases, and is implicated in AD (49, 50). This process may lead to enhanced activation of calpains (51). This in turn could influence a number of pathologic processes, including tau proteolysis. Indeed, tau has a number of putative calpain cleavage sites, and incubation of recombinant tau with calpain generates specific fragments, including one that is ∼35 kDa and one that is ∼17 kDa (19, 20). PubMed:24027553