Involvement of Akt in neurite outgrowth

Read, Danielle E.; Gorman, Adrienne M.

doi:10.1007/s00018-009-0057-8

Cited by 186 publications

(152 citation statements)

References 92 publications

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…Coffee-induced reduction of Akt phosphorylation may be responsible for the reduction of BDNF gene expression. Neurite outgrowth is one of the downstream effects of the Akt/CREB signaling cascade [30]. In this study, we showed that coffee significantly reduced the BDNF-induced neurite outgrowth.…”

Section: Discussionsupporting

confidence: 48%

Coffee Modulates the Function of Brain-Derived Neurotrophic Factor (BDNF) in Human Neuroblastoma SH-SY5Y Cells

Kakio¹,

Nakazawa²,

Funakoshi‐Tago³

et al. 2015

View full text Add to dashboard Cite

Recent epidemiological studies showed that daily coffee consumption is associated with a lower risk for several neurological disorders such as Alzheimer's disease and Parkinson's disease; however, the molecular mechanisms responsible for the protective effect of coffee against neurological disorders have not been elucidated. As brain-derived neurotrophic factor (BDNF) promotes neuronal survival and protects against neuronal damage, we investigated the effects of coffee on BDNF signaling using human neuroblastoma SH-SY5Y cells. We found that brewed coffee exerted an inhibitory effect on the autophosphorylation of tropomyosin receptor kinase B (TrkB), a BDNF receptor. Additionally, coffee reduced the phosphorylation of Akt in BDNF-treated SH-SY5Y cells. Treatment with coffee did not affect the TrkB receptor on the cell surface. The major constituents of coffee, such as caffeine, caffeic acid, chlorogenic acid, and trigonelline had no effect on TrkB phosphorylation induced by BDNF. In addition, coffee reduced the BDNF-induced increase in BDNF gene expression and the neurite outgrowth promoted by BDNF. Our data suggest that the protective effect of coffee reported in epidemiological studies against neurological disorders may not be associated with BDNF signaling through TrkB.

show abstract

Section: Discussionsupporting

confidence: 48%

Coffee Modulates the Function of Brain-Derived Neurotrophic Factor (BDNF) in Human Neuroblastoma SH-SY5Y Cells

Kakio¹,

Nakazawa²,

Funakoshi‐Tago³

et al. 2015

View full text Add to dashboard Cite

show abstract

“…*Po0.05, **Po0.005; Student's paired t-test Trib3 mediates death of NGF-deprived neurons N Zareen et al sparing effects we observed in Trib3 knockdown on processes of NGF-deprived neurons. 47 PI3K and Akt activation is a key pathway by which NGF promotes survival and NGF withdrawal reduces PI3K activity and Akt phosphorylation. [1][2][3]5 Why then are Trib3 and its actions on Akt required for neuron death after NGF deprivation?…”

Section: Discussionmentioning

confidence: 99%

A feed-forward loop involving Trib3, Akt and FoxO mediates death of NGF-deprived neurons

2013

View full text Add to dashboard Cite

The mechanisms governing neuron death following NGF deprivation are incompletely understood. Here, we show that Trib3, a protein induced by NGF withdrawal, has a key role in such death via a loop involving the survival kinase Akt and FoxO transcription factors. Trib3 overexpression is sufficient to induce neuron death, and silencing of endogenous Trib3 strongly protects from death when NGF is withdrawn. Mechanism studies reveal that Trib3 interferes with phosphorylation/activity of Akt and contributes to Akt inactivation after NGF deprivation. FoxO1a, a direct Akt substrate, is dephosphorylated upon NGF withdrawal and consequently undergoes nuclear translocation and activates pro-apoptotic genes. We find that Trib3 is required for FoxO1a dephosphorylation and nuclear translocation after NGF deprivation. Conversely, Trib3 induction requires FoxO transcription factors, which show enhanced occupancy of the Trib3 promoter region following NGF withdrawal. Collectively, these findings support a mechanism in which NGF deprivation, Akt dephosphorylation/inactivation, FoxO dephosphorylation/ activation and Trib3 induction are linked in a self-amplifying feed-forward loop that culminates in neuron death.

show abstract

“…Our results are summarized in Figure 8, which A previous report has demonstrated that pravastatin's stimulation of neurite outgrowth is mediated by reduction of RhoA signaling via inhibition of geranylgeranylation [12] . In addition to the Rho family proteins [31] , Akt has been revealed as a key mediator of several aspects of neurite outgrowth, including elongation, branching and caliber [15] . Several in vitro and in vivo studies provided evidence that statins activate the PKB/Akt pathway [3,32,33] .…”

Section: Discussionmentioning

confidence: 99%

“…Akt is the major effector of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Downstream of Akt, several substrates have been identified that are likely to play key roles in Akt-mediated neurite outgrowth, such as mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3β (GSK-3β) [15] . mTOR is a serine/threonine protein kinase that regulates multiple cellular functions including neurite outgrowth.…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3β signaling pathways

et al. 2012

View full text Add to dashboard Cite

Aim: To investigate whether atorvastatin can promote formation of neurites in cultured cortical neurons and the signaling mechanisms responsible for this effect. Methods: Cultured rat cerebral cortical neurons were incubated with atorvastatin (0.05-10 μmol/L) for various lengths of time. For pharmacological experiments, inhibitors were added 30 min prior to addition of atorvastatin. Control cultures received a similar amount of DMSO. Following the treatment period, phase-contrast digital images were taken. Digital images of neurons were analyzed for total neurite branch length (TNBL), neurite number, terminal branch number, and soma area by SPOT Advanced Imaging software. After incubation with atorvastatin for 48 h, the levels of phosphorylated 3-phosphoinoside-dependent protein kinase-1 (PDK1), phospho-Akt, phosphorylated mammalian target of rapamycin (mTOR), phosphorylated 4E-binding protein 1 (4E-BP1), p70S6 kinase (p70S6K), and glycogen synthase kinase-3β (GSK-3β) in the cortical neurons were evaluated using Western blotting analyses. Results: Atorvastatin (0.05-10 µmol/L) resulted in dose-dependent increase in neurite number and length in these neurons. Pretreatment of the cortical neurons with phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 (30 µmol/L) and wortmannin (5 µmol/L), Akt inhibitor tricribine (1 µmol/L) or mTOR inhibitor rapamycin (100 nmol/L) blocked the atorvastatin-induced increase in neurite outgrowth, suggesting that atorvastatin promoted neurite outgrowth via activating the PI3K/Akt/mTOR signaling pathway. Atorvastatin (10 µmol/L) significantly increased the levels of phosphorylated PDK1, Akt and mTOR in the cortical neurons, which were prevented by LY294002 (30 µmol/L). Moreover, atorvastatin (10 µmol/L) stimulated the phosphorylation of 4E-BP1 and p70S6K, the substrates of mTOR, in the cortical neurons. In addition, atorvastatin (10 µmol/L) significantly increased the phosphorylated GSK-3β level in the cortical neurons, which was prevented by both LY294002 and tricribine. Conclusion: These results suggest that activation of both the PI3K/Akt/mTOR and Akt/GSK-3β signaling pathways is responsible for the atorvastatin-induced neurite outgrowth in cultured cortical neurons.

show abstract

Involvement of Akt in neurite outgrowth

Cited by 186 publications

References 92 publications

Coffee Modulates the Function of Brain-Derived Neurotrophic Factor (BDNF) in Human Neuroblastoma SH-SY5Y Cells

Coffee Modulates the Function of Brain-Derived Neurotrophic Factor (BDNF) in Human Neuroblastoma SH-SY5Y Cells

A feed-forward loop involving Trib3, Akt and FoxO mediates death of NGF-deprived neurons

Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3β signaling pathways

Contact Info

Product

Resources

About