ArticleNeurobiology of disease2009
A cellular model of Alzheimer's disease therapeutic efficacy: PKC activation reverses Abeta-induced biomarker abnormality on cultured fibroblasts.
Article in Neurobiology of disease, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 64 citations in OpenAlex.
- Exploring the skin as an open window onto neurodegenerative diseases.Translational neurodegeneration · 2025Review
- Regulatory role of LncRNA FMR1-AS1 in the pathogenesis of alzheimer's disease based on bioinformatics and in vitro experimental validation.Scientific reports · 2025Article
- Targeting signaling pathways in neurodegenerative diseases: Quercetin's cellular and molecular mechanisms for neuroprotection.Animal models and experimental medicine · 2025Review
- Protein Kinase C (PKC) in Neurological Health: Implications for Alzheimer's Disease and Chronic Alcohol Consumption.Brain sciences · 2024Review
- Developing Biomarkers for the Skin: Biomarkers for the Diagnosis and Prediction of Treatment Outcomes of Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Reactivity of Thiol-Rich Zn Sites in Diacylglycerol-Sensing PKC C1 Domain Probed by NMR Spectroscopy.Frontiers in molecular biosciences · 2021Article
- Human Autopsy-Derived Scalp Fibroblast Biobanking for Age-Related Neurodegenerative Disease Research.Cells · 2020Article
- The Implications for Cells of the Lipid Switches Driven by Protein-Membrane Interactions and the Development of Membrane Lipid Therapy.International journal of molecular sciences · 2020Review
- Evaluation of Toxic Amyloid 42 Oligomers in Rat Primary Cerebral Cortex Cells and Human iPS-derived Neurons Treated with 10-Me-Aplog-1, a New PKC Activator.International journal of molecular sciences · 2020Article
- Alzheimer's disease mechanisms in peripheral cells: Promises and challenges.Alzheimer's & dementia (New York, N. Y.) · 2019Article
- Inhibition of PKCδ reduces amyloid-β levels and reverses Alzheimer disease phenotypes.The Journal of experimental medicine · 2018Article
- Article
- Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents.Journal of cellular physiology · 2018Article
- Molecular dynamics simulations reveal ligand-controlled positioning of a peripheral protein complex in membranes.Nature communications · 2017Article
- Simplified Bryostatin Analogues Protect Cells from Chikungunya Virus-Induced Cell Death.Journal of natural products · 2016Article
- The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer's disease.Future science OA · 2015Review
- Protein kinase C is essential for viability of the rice blast fungus Magnaporthe oryzae.Molecular microbiology · 2015Article
- Conformation-activity relationships of polyketide natural products.Natural product reports · 2015Review
- Studies on the regio- and diastereo-selective epoxidation of daphnanes and tiglianes.Tetrahedron letters · 2015Article
- Toward a biorelevant structure of protein kinase C bound modulators: design, synthesis, and evaluation of labeled bryostatin analogues for analysis with rotational echo double resonance NMR spectroscopy.Journal of the American Chemical Society · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
PKC signaling is critical for the non-toxic degradation of amyloid precursor protein (APP) and inhibition of GSK3beta, which controls phosphorylation of tau protein in Alzheimer's disease (AD). Thus the misregulation of PKC signaling could contribute to the origins of AD. Bryostatin, a potent PKC modulator, has the potential to ameliorate both the neurodegeneration and the recent memory loss associated with AD. As reported herein bryostatin and a potent synthetic analog (picolog) are found to cause stimulation of non-amyloidogenic pathways by increasing alpha-secretase activity and thus lowering the amount of toxic Abeta produced. Both bryostatin and picolog increased the secretion of the alpha-secretase product (s-APP-alpha) of APP at sub-nanomolar to nanomolar concentrations. A peripheral AD-Biomarker has previously been autopsy-validated. This Biomarker, based on bradykinin-induced differential phosphorylation of Erk1 and Erk2, has been used here to test the therapeutic efficacy both for bryostatin and picolog. Both of these PKC activators are then shown to convert the AD Erk1/2 phenotype of fibroblasts into the phenotype of "normal" control skin fibroblasts. This conversion occurred for both the abnormal Erk1/2 phenotype induced by application of Abeta(1-42) to the fibroblasts or the phenotype observed for fibroblasts of AD patients. The Abeta(1-42)-induction, and PKC modulator reversal of the AD Erk1/2 biomarker phenotype demonstrate the AD-Biomarker's potential to monitor both disease progression and treatment response. Additionally, this first demonstration of the therapeutic potential in AD of a synthetically accessible bryostatin analog warrants further preclinical advancement.
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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.