ArticleProceedings of the National Academy of Sciences of the United States of America2004
Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 337 citations in OpenAlex.
- Natural Compounds for Alzheimer's Disease Therapy: A Systematic Review of Preclinical and Clinical Studies.International journal of molecular sciences · 2019Pooled it
- Current and emerging drug treatment options for Alzheimer's disease: a systematic review.Drugs · 2011Pooled it
- The Ubiquitin-Proteasome System in Brain Disorders: Pathogenic Pathways, Post-Translational Tweaks, and Therapeutic Frontiers.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Article
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- Elevated CSF GAP-43 in Mild Cognitive Impairment Linked to Cognitive Impairment Through Increased Amyloid-β Accumulation, with a Shift to Reduced Amyloid-β Accumulation in Alzheimer's Disease.Journal of molecular neuroscience : MN · 2025Article
- Advanced Technologies for Large Scale Supply of Marine Drugs.Marine drugs · 2025Review
- A Valuable Target for Therapy: The Metalloproteinase ADAM10.Current protein & peptide science · 2025Review
- Single-microglia transcriptomic transition network-based prediction and real-world patient data validation identifies ketorolac as a repurposable drug for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- An insight into the concept of neuroinflammation and neurodegeneration in Alzheimer's disease: targeting molecular approach Nrf2, NF-κB, and CREB.Inflammopharmacology · 2024Review
- Therapeutic effects of a novel synthetic α-secretase.Frontiers in aging neuroscience · 2024Article
- The ε-Isozyme of Protein Kinase C (PKCε) Is Impaired in ALS Motor Cortex and Its Pulse Activation by Bryostatin-1 Produces Long Term Survival in Degenerating SOD1-G93A Motor Neuron-like Cells.International journal of molecular sciences · 2023Article
- Synthesis and evaluation of DAG-lactone derivatives with HIV-1 latency reversing activity.European journal of medicinal chemistry · 2023Article
- Role of A-Kinase Anchoring Protein 12 in the Central Nervous System.Journal of clinical neurology (Seoul, Korea) · 2023Review
- New Insights into Alzheimer's Disease: Novel Pathogenesis, Drug Target and Delivery.Pharmaceutics · 2023Review
- Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations.International journal of molecular sciences · 2023Article
- Cellular response to β-amyloid neurotoxicity in Alzheimer's disease and implications in new therapeutics.Animal models and experimental medicine · 2023Review
- Therapeutic Potential of Natural Compounds in Neurodegenerative Diseases: Insights from Clinical Trials.Pharmaceutics · 2023Review
- Bryostatin-1: a promising compound for neurological disorders.Frontiers in pharmacology · 2023Review
- Decoding brain memory formation by single-cell RNA sequencing.Briefings in bioinformatics · 2022Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) characteristically presents with early memory loss. Regulation of K(+) channels, calcium homeostasis, and protein kinase C (PKC) activation are molecular events that have been implicated during associative memory which are also altered or defective in AD. PKC is also involved in the processing of the amyloid precursor protein (APP), a central element in AD pathophysiology. In previous studies, we demonstrated that benzolactam (BL), a novel PKC activator, reversed K(+) channels defects and enhanced secretion of APP alpha in AD cells. In this study we present data showing that another PKC activator, bryostatin 1, at subnanomolar concentrations dramatically enhances the secretion of the alpha-secretase product sAPP alpha in fibroblasts from AD patients. We also show that BL significantly increased the amount of sAPP alpha and reduced A beta 40 in the brains of APP[V717I] transgenic mice. In a more recently developed AD double-transgenic mouse, bryostatin was effective in reducing both brain A beta 40 and A beta 42. In addition, bryostatin ameliorated the rate of premature death and improved behavioral outcomes. Collectively, these data corroborate PKC and its activation as a potentially important means of ameliorating AD pathophysiology and perhaps cognitive impairment, thus offering a promising target for drug development. Because bryostatin 1 is devoid of tumor-promoting activity and is undergoing numerous clinical studies for cancer treatment in humans, it might be readily tested in patients as a potential therapeutic agent for Alzheimer's disease.
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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.