ArticleProceedings of the National Academy of Sciences of the United States of America2011
Constitutive cAMP response element binding protein (CREB) activation by Alzheimer's disease presenilin-driven inositol trisphosphate receptor (InsP3R) Ca2+ signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 86 citations in OpenAlex.
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- Abnormal calcium activity and CREB phosphorylation are associated with motor memory impairment in presenilin-1 mutant knock-in mice.Cell calcium · 2025Article
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- Muscarinic acetylcholine receptor-dependent and NMDA receptor-dependent LTP and LTD share the common AMPAR trafficking pathway.iScience · 2023Article
- Neuroprotective Effects of a Multi-Herbal Extract on Axonal and Synaptic DisruptionJournal of Alzheimer's disease reports · 2023Article
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
- Elevating the Levels of Calcium Ions Exacerbate Alzheimer's Disease via Inducing the Production and Aggregation of β-Amyloid Protein and Phosphorylated Tau.International journal of molecular sciences · 2021Review
- The Calcium/Calmodulin-Dependent Kinases II and IV as Therapeutic Targets in Neurodegenerative and Neuropsychiatric Disorders.International journal of molecular sciences · 2021Review
- Development of novel phosphodiesterase 5 inhibitors for the therapy of Alzheimer's disease.Biochemical pharmacology · 2020Review
- Chrysophanol improves memory ability of d-galactose and Aβ3 Biotech · 2020Article
- The Regulating Mechanism of Chrysophanol on Protein Level of CaM-CaMKIV to Protect PC12 Cells Against AβDrug design, development and therapy · 2020Article
- Synaptic and memory dysfunction induced by tau oligomers is rescued by up-regulation of the nitric oxide cascade.Molecular neurodegeneration · 2019Article
- CREB signals as PBMC-based biomarkers of cognitive dysfunction: A novel perspective of the brain-immune axis.Brain, behavior, and immunity · 2019Review
- High-Frequency Repetitive Magnetic Stimulation Enhances the Expression of Brain-Derived Neurotrophic Factor Through Activation of CaFrontiers in neurology · 2018Article
- Cyclic nucleotide signaling changes associated with normal aging and age-related diseases of the brain.Cellular signalling · 2018Review
- Genistein protects hippocampal neurons against injury by regulating calcium/calmodulin dependent protein kinase IV protein levels in Alzheimer's disease model rats.Neural regeneration research · 2017Article
- Targeted Downregulation of dMyc Suppresses Pathogenesis of Human Neuronal Tauopathies in Drosophila by Limiting Heterochromatin Relaxation and Tau Hyperphosphorylation.Molecular neurobiology · 2017Article
- CDK5 downregulation enhances synaptic plasticity.Cellular and molecular life sciences : CMLS · 2017Article
- Cognitive dysfunction in major depression and Alzheimer's disease is associated with hippocampal-prefrontal cortex dysconnectivity.Neuropsychiatric disease and treatment · 2017Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in presenilins (PS) account for most early-onset familial Alzheimer's disease (FAD). Accumulating evidence suggests that disrupted Ca(2+) signaling may play a proximal role in FAD specifically, and Alzheimer's disease (AD) more generally, but its links to the pathogenesis of AD are obscure. Here we demonstrate that expression of FAD mutant PS constitutively activates the transcription factor cAMP response element binding protein (CREB) and CREB target gene expression in cultured neuronal cells and AD mouse models. Constitutive CREB activation was associated with and dependent on constitutive activation of Ca(2+)/CaM kinase kinase β and CaM kinase IV (CaMKIV). Depletion of endoplasmic reticulum Ca(2+) stores or plasma membrane phosphatidylinositol-bisphosphate and pharmacologic inhibition or knockdown of the expression of the inositol trisphosphate receptor (InsP(3)R) Ca(2+) release channel each abolished FAD PS-associated constitutive CaMKIV and CREB phosphorylation. CREB and CaMKIV phosphorylation and CREB target gene expression, including nitric oxide synthase and c-fos, were enhanced in brains of M146V-KI and 3xTg-AD mice expressing FAD mutant PS1 knocked into the mouse locus. FAD mutant PS-expressing cells demonstrated enhanced cell death and sensitivity to Aβ toxicity, which were normalized by interfering with the InsP(3)R-CAMKIV-CREB pathway. Thus, constitutive CREB phosphorylation by exaggerated InsP(3)R Ca(2+) signaling in FAD PS-expressing cells may represent a signaling pathway involved in the pathogenesis of AD.
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