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NGF increases the amount of APP. 30 / 31
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"In PC12 cells, a rat pheochromocytoma cell line, we have demonstrated that nerve growth factor (NGF) induces the APP gene expression and increases APP mRNA levels in the presence of 0.5 or 15% serum."
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"These data suggest that, NGF may elevate APP levels in part through enhanced translation."
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"However, NGF has been reported to upregulate expression of the beta-amyloid precursor protein, which in turn could accelerate deposition of " mature " beta-amyloid in the brain."
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"The association of alterations in beta APP gene expression with AD like neuropathological changes and cognitive impairment in animals, and with AD like neurodegeneration in Down syndrome patients suggests that NGF mediated increases in beta APP expression could negate or attenuate NGF 's neurotrophic activity in AD treatment trials."
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"In this study, we investigated the effects of antisense oligonucleotide (AO) on the overexpression of APP induced by IL-1beta and NGF."
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"However, NGF induced secretion of sAPP is unaffected by the dominant negative ras, implying that the sAPP release elicited by NGF is independent of the stimulation of APP expression by NGF in PC12 cel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"These results demonstrate that NGF increases APP gene expression at transcriptional level."
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"These findings lead us to hypothesize that APP and TrkA only form a complex when APP is not phosphorylated at the T668 site and that, in turn, the reduction in the APP pT668 level induced by NGF facilitates TrkA binding to APP."
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"While NGF did increase APP protein levels, steady-state APP mRNA levels were decreased in NGF treated PC12 cells."
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"The present study demonstrates that the NGF mediated increase in APP protein levels is not due to enhanced mRNA or protein stability and that NO, which is necessary for NGF induced neurite outgrowth and increased APP protein levels in PC12 cells, modulates APP mRNA levels and protein stability."
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"Based on these data we propose that in PC12 cells, NGF increases APP levels through enhanced translation rate and that NO, which modulates the NGF induced increase in APP protein, also regulates APP mRNA levels and could play a role in APP processing."
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"Since NGF did not increase the levels of APP mRNA or protein stability, our findings suggest that in PC12 cells NGF increases APP protein expression through enhanced transcription, followed by rapid translation and degradation of APP mRNA."
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"The levels of all three isoforms of nitric oxide synthase (NOS) are also increased following treatment with NGF [XREF_BIBR, XREF_BIBR] and we found that NOS inhibitors attenuate the increase in APP protein levels caused by NGF [XREF_BIBR]."
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"However, in vivo administration of NGF to the developing hamster brain was shown to induce the expression of the beta-amyloid precursor protein (beta APP) gene."
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"Nerve growth factor (NGF), a neurotrophin reported to benefit AD patients [XREF_BIBR], has also been found to modulate the levels and post-translational processing of APP."
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"NGF increased in a dose dependent fashion neurite outgrowth, APP mRNA expression, and APP secretion with maximal effects at concentrations known to saturate TrkA receptor binding."
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"In vitro studies using neuronal PC12 cells have successfully shown that APP gene expression is modulated by NGF, and an increase in APP expression is noted upon its withdrawal [XREF_BIBR]."
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"PC12 cells were treated with either the non selective NOS inhibitor N (omega)-nitro-L-arginine methylester (L-NAME) or the inducible NOS selective inhibitor s-methylisothiourea (S-MIU), and the effect on NGF mediated increases in APP expression was determined."
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"The combined use of APP antisense oligonucleotides and neurotrophic agents may find clinical utility in the treatment of Alzheimer-type dementia since it is known that NGF normally causes increases in APP levels."
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"Epidermal, basic fibroblast and nerve growth factors (EGF, bFGF and NGF) have all been shown to induce APP expression in cell culture (Refolo et al., 1989; Quon et al., 1990) and NGF also increases AP[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"We have previously described that NGF increases APP mRNA levels in PC12 cells."
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"NGF significantly increased total APP protein levels following 96 h of treatment and this increase was prevented in cells pre-treated with S-MIU."
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"In fact, it was shown that NGF acts on the APP promoter mediated by p75 NTR and upregulates APP transcription and the secretion of secreted amyloid precursor protein (sAPP), although intraparenchymal NGF delivery did not significantly increase Abeta deposition in monkeys."
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"Since APP mediates neurite outgrowth and axonal transport of neurons [23,31], it is likely that APP expression in DRG neurons is increased by NGF for promoting neuritic (axonal) differentiation."
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"Using phosphorothioate-oligonucleotides against initiation codon significantly reduced the protein levels of APP induced by NGF and IL-1beta to basal level in PC12 cell culture systems."
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"These results suggest that ras mediates the induction of APP gene expression by NGF and other ligands of tyrosine kinase receptors."
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"However, recent findings suggest that NGF upregulates the expression of amyloid pre- cursor protein, a cleavage product which accumu- lates in AD (Mobley et al., 1988)."
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"The recovery from the immuno-lesion was obtained by transplanting nerve growth factor (NGF)-secreting fibroblasts that restored altered cholinergic markers (ChAT and M 1 receptor density) and NGF trea[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Taken together, these findings suggest the enhanced transcription of APP induced by NGF is followed by rapid translation and degradation of APP mRNA."
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"Our initial findings agreed with previous reports [XREF_BIBR - XREF_BIBR] and indicated that the NGF mediated increase in APP protein levels was due to increased APP transcription however, the data in the present study suggest that this enhanced transcription does not result in increased APP mRNA levels."
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