ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Wild-type but not FAD mutant presenilin-1 prevents neuronal degeneration by promoting phosphatidylinositol 3-kinase neuroprotective signaling.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- Glycogen synthase kinase 3 (GSK3) inhibition: a potential therapeutic strategy for Alzheimer's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- PS1 FAD mutants decrease ephrinB2-regulated angiogenic functions, ischemia-induced brain neovascularization and neuronal survival.Molecular psychiatry · 2021Article
- Deregulation of signalling in genetic conditions affecting the lysosomal metabolism of cholesterol and galactosyl-sphingolipids.Neurobiology of disease · 2020Review
- Aβ40 Oligomers Promote Survival and Early Neuronal Differentiation of Dentate Gyrus-Isolated Precursor Cells Through Activation of the Akt Signaling Pathway.Neurotoxicity research · 2020Article
- Decreased Deposition of Beta-Amyloid 1-38 and Increased Deposition of Beta-Amyloid 1-42 in Brain Tissue of Presenilin-1 E280A Familial Alzheimer's Disease Patients.Frontiers in aging neuroscience · 2020Article
- Curcumin Ameliorates the Impaired Insulin Signaling Involved in the Pathogenesis of Alzheimer's Disease in Rats.Journal of Alzheimer's disease reports · 2019Article
- Implications of PI3K/AKT/PTEN Signaling on Superoxide Dismutases Expression and in the Pathogenesis of Alzheimer's Disease.Diseases (Basel, Switzerland) · 2018Review
- Presenilin1/γ-secretase protects neurons from glucose deprivation-induced death by regulating miR-212 and PEA15.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Fibroblast growth factor rescues brain endothelial cells lacking presenilin 1 from apoptotic cell death following serum starvation.Scientific reports · 2016Article
- Reduction of increased calcineurin activity rescues impaired homeostatic synaptic plasticity in presenilin 1 M146V mutant.Neurobiology of aging · 2015Article
- G206D Mutation of Presenilin-1 Reduces Pen2 Interaction, Increases Aβ42/Aβ40 Ratio and Elevates ER Ca(2+) Accumulation.Molecular neurobiology · 2015Article
- Presenilin 1 is necessary for neuronal, but not glial, EGFR expression and neuroprotection via γ-secretase-independent transcriptional mechanisms.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Early etiology of Alzheimer's disease: tipping the balance toward autophagy or endosomal dysfunction?Acta neuropathologica · 2015Review
- Presenilin-1 regulates the expression of p62 to govern p62-dependent tau degradation.Molecular neurobiology · 2014Article
- Cell signaling abnormalities may drive neurodegeneration in familial Alzheimer disease.Neurochemical research · 2014Review
- Amyloid beta-induced glycogen synthase kinase 3β phosphorylated VDAC1 in Alzheimer's disease: implications for synaptic dysfunction and neuronal damage.Biochimica et biophysica acta · 2013Review
- Presenilin-1/γ-secretase controls glutamate release, tyrosine phosphorylation, and surface expression of N-methyl-D-aspartate receptor (NMDAR) subunit GluN2B.The Journal of biological chemistry · 2013Article
- Presenilin mediates neuroprotective functions of ephrinB and brain-derived neurotrophic factor and regulates ligand-induced internalization and metabolism of EphB2 and TrkB receptors.Neurobiology of aging · 2013Article
- Telencephalin protects PAJU cells from amyloid beta protein-induced apoptosis by activating the ezrin/radixin/moesin protein family/phosphatidylinositol-3-kinase/protein kinase B pathway.Neural regeneration research · 2012Article
- Advances in the pathogenesis of Alzheimer's disease: a re-evaluation of amyloid cascade hypothesis.Translational neurodegeneration · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The role of presenilin-1 (PS1) in neuronal phosphatidylinositol 3-kinase (PI3K)/Akt signaling was investigated in primary neuronal cultures from wild-type (WT) and PS1 null (PS1-/-) embryonic mouse brains. Here we show that in PS1-/- cultures, the onset of neuronal maturation coincides with a decrease in the PI3K-dependent phosphorylation-activation of Akt and phosphorylation-inactivation of glycogen synthase kinase-3 (GSK-3). Mature PS1-/- neurons show increased activation of apoptotic caspase-3 and progressive degeneration preceded by dendritic retraction. Expression of exogenous WT PS1 or constitutively active Akt in PS1-/- neurons stimulates PI3K signaling and suppresses both caspase-3 activity and dendrite retraction. The survival effects of PS1 are sensitive to inhibitors of PI3K kinase but insensitive to gamma-secretase inhibitors. Familial Alzheimer disease (FAD) mutations suppress the ability of PS1 to promote PI3K/AKT signaling, prevent phosphorylation/inactivation of GSK-3 and promote activation of caspase-3. These mutation effects are reversed upon coexpression of constitutively active Akt. Together, our data indicate that the neuroprotective role of PS1 depends on its ability to activate the PI3K/Akt signaling pathway and that PS1 FAD mutations increase GSK-3 activity and promote neuronal apoptosis by inhibiting the function of PS1 in this pathway. These observations suggest that stimulation of PI3K/Akt signaling may be beneficial to FAD patients.
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