ArticleThe Journal of experimental medicine2018
Inhibition of PKCδ reduces amyloid-β levels and reverses Alzheimer disease phenotypes.
Article in The Journal of experimental medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Efficacy and safety of 3-n-butylphthalide for the treatment of cognitive impairment: A systematic review and meta-analysis.CNS neuroscience & therapeutics · 2022Pooled it
- Protein Kinase C-delta (PKCδ) in Neurodegeneration and Cerebral Ischemia: Molecular Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Targeting protein kinase C signaling cascades in alzheimer's disease: emerging neuroprotective roles of aurothioglucose.Inflammopharmacology · 2026Review
- Regulation of selective class switching provides long-term therapeutic benefits for hay fever.JCI insight · 2025Article
- Comprehensive Genome-Wide Analysis of Shared Genetic Factors in Gastrointestinal and Neurodegenerative Diseases.Brain and behavior · 2025Article
- Chronic hypoxia induces liver injury via PKCδ/ASMase-driven ceramide accumulation and endoplasmic reticulum stress in rats.Lipids in health and disease · 2025Article
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- PKCδ Regulates DNA Damage and Cell Death through a SIRT6/Nrf2-dependent Antioxidant Response.Molecular cancer research : MCR · 2025Article
- Unraveling the Role of Autotaxin and Lysophosphatidic Acid in Alzheimer's Disease: From Molecular Mechanisms to Therapeutic Potential.International journal of molecular sciences · 2025Review
- Article
- PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases.Communications biology · 2025Review
- Rottlerin Enhances the Autophagic Degradation of Phosphorylated Tau in Neuronal Cells.Molecular neurobiology · 2024Article
- Article
- Protein Kinase C-Delta Mediates Cell Cycle Reentry and Apoptosis Induced by Amyloid-Beta Peptide in Post-Mitotic Cortical Neurons.International journal of molecular sciences · 2024Article
- PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- PKCδ is an activator of neuronal mitochondrial metabolism that mediates the spacing effect on memory consolidation.bioRxiv : the preprint server for biology · 2024Article
- Protein Kinase C (PKC) in Neurological Health: Implications for Alzheimer's Disease and Chronic Alcohol Consumption.Brain sciences · 2024Review
- The roles of RACK1 in the pathogenesis of Alzheimer's disease.Journal of biomedical research · 2024Article
- What Threshold of Amyloid Reduction Is Necessary to Meaningfully Improve Cognitive Function in Transgenic Alzheimer's Disease Mice?Journal of Alzheimer's disease reports · 2024Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
β-amyloid protein (Aβ) plays a central role in the pathogenesis of Alzheimer disease (AD). Aβ is generated from sequential cleavage of amyloid precursor protein (APP) by β-site APP-cleaving enzyme 1 (BACE1) and the γ-secretase complex. Although activation of some protein kinase C (PKC) isoforms such as PKCα and ε has been shown to regulate nonamyloidogenic pathways and Aβ degradation, it is unclear whether other PKC isoforms are involved in APP processing/AD pathogenesis. In this study, we report that increased PKCδ levels correlate with BACE1 expression in the AD brain. PKCδ knockdown reduces BACE1 expression, BACE1-mediated APP processing, and Aβ production. Conversely, overexpression of PKCδ increases BACE1 expression and Aβ generation. Importantly, inhibition of PKCδ by rottlerin markedly reduces BACE1 expression, Aβ levels, and neuritic plaque formation and rescues cognitive deficits in an APP Swedish mutations K594N/M595L/presenilin-1 with an exon 9 deletion-transgenic AD mouse model. Our study indicates that PKCδ plays an important role in aggravating AD pathogenesis, and PKCδ may be a potential target in AD therapeutics.
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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.