ArticleJournal of neurochemistry2007
Down-regulation of cAMP-dependent protein kinase by over-activated calpain in Alzheimer disease brain.
Article in Journal of neurochemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 136 citations in OpenAlex.
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- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Development of a brain-penetrant G9a methylase inhibitor to target Alzheimer's disease-associated proteopathology.Nature communications · 2025Article
- Phosphodiesterase 4 Inhibition in Neuropsychiatric Disorders Associated with Alzheimer's Disease.Cells · 2025Review
- PDE10A as a novel diagnostic and therapeutic target in cancer: insights and challenges.Frontiers in oncology · 2025Review
- Evaluating the Role of N-Acetyl-L-Tryptophan in the Aβ 1-42-Induced Neuroinflammation and Cognitive Decline in Alzheimer's Disease.Molecular neurobiology · 2024Article
- Dissecting the shared genetic architecture between Alzheimer's disease and frailty: a cross-trait meta-analyses of genome-wide association studies.Frontiers in genetics · 2024Article
- miR-200a-3p Regulates PRKACB and Participates in Aluminium-Induced Tau Phosphorylation in PC12 Cells.Neurotoxicity research · 2022Article
- The neuroprotective effects of glucagon-like peptide 1 in Alzheimer's and Parkinson's disease: An in-depth review.Frontiers in neuroscience · 2022Review
- Discovery of putative inhibitors against main drivers of SARS-CoV-2 infection: Insight from quantum mechanical evaluation and molecular modeling.Frontiers in chemistry · 2022Article
- Reversing Alzheimer's disease dementia with clemastine, fingolimod, or rolipram, plus anti-amyloid therapy.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Temporal Quantitative Profiling of Newly Synthesized Proteins during Aβ Accumulation.Journal of proteome research · 2021Article
- Phosphodiesterase Inhibitors for Alzheimer's Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale.Journal of Alzheimer's disease reports · 2020Review
- The novel GLP-1/GIP analogue DA5-CH reduces tau phosphorylation and normalizes theta rhythm in the icv. STZ rat model of AD.Brain and behavior · 2020Article
- Morin attenuates high-fat diet induced-obesity related vascular endothelial dysfunction in Wistar albino rats.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- Knockout of p75 neurotrophin receptor attenuates the hyperphosphorylation of Tau in pR5 mouse model.Aging · 2019Article
- Clioquinol: To harm or heal.Pharmacology & therapeutics · 2019Review
- Involvement of calpain in the neuropathogenesis of Alzheimer's disease.Medicinal research reviews · 2019Review
- Liraglutide and its Neuroprotective Properties-Focus on Possible Biochemical Mechanisms in Alzheimer's Disease and Cerebral Ischemic Events.International journal of molecular sciences · 2019Review
- Granisetron Alleviates Alzheimer's Disease Pathology in TgSwDI Mice Through Calmodulin-Dependent Protein Kinase II/cAMP-Response Element Binding Protein Pathway.Journal of Alzheimer's disease : JAD · 2019Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Impaired cognition and memory may be associated with down-regulation of cAMP-response element-binding protein (CREB) in the brain in patients with Alzheimer disease, but the molecular mechanism leading to the down-regulation is not understood. In this study, we found a selective reduction in the levels of the regulatory subunits (RIIalpha and RIIbeta) and the catalytic subunit (Cbeta) as well as the enzymatic activity of cAMP-dependent protein kinase (PKA), which is the major positive regulator of CREB. We also observed that PKA subunits were proteolyzed by calpain and the levels of PKA subunits correlated negatively with calpain activation in the human brain. These findings led us to propose that in the brain in patients with Alzheimer disease, over-activation of calpain because of calcium dysregulation causes increased degradation and thus decreased activity of PKA, which, in turn, contributes to down-regulation of CREB and impaired cognition and memory.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.