ArticleScience signaling2016
Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer's disease.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 63 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
63 citing papers in PubMed, 3 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Gene co-expression changes underlying the functional connectomic alterations in Alzheimer's disease.BMC medical genomics · 2022Pooled it
- Sex-specific DNA methylation differences in Alzheimer's disease pathology.Acta neuropathologica communications · 2021Pooled it
- A Meta-Analysis of Brain DNA Methylation Across Sex, Age, and Alzheimer's Disease Points for Accelerated Epigenetic Aging in Neurodegeneration.Frontiers in aging neuroscience · 2021Pooled it
- Recent advances in MOF-phosphate interaction-based bioanalysis: from enrichment to sensing.Mikrochimica acta · 2026Review
- Alzheimer's Pathology Enhances Excitatory Synaptic Input and Integration in VTA Dopamine Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- CSF proteomic profiling with amyloid and tau pathology identifies distinctive sex-specific alteration of multiple proteins involved in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Gene-Exercise Interactions in Amyloid Metabolism and Clearance: Implications for Alzheimer's Disease.International journal of molecular sciences · 2025Review
- PKC-dependent enhancement of glutamate input to VTA dopamine neurons in 3xTg-AD mice.bioRxiv : the preprint server for biology · 2025Article
- Heat shock proteins function as signaling molecules to mediate neuron-glia communication in C. elegans during aging.Nature neuroscience · 2025Article
- Uncovering active ingredients and mechanisms of Pholiota adiposa in the treatment of Alzheimer's disease based on network pharmacology and bioinformatics.Scientific reports · 2025Article
- A PKCη missense mutation enhances Golgi-localized signaling and is associated with recessively inherited familial Alzheimer's disease.Science signaling · 2025Article
- Article
- Protein kinase C eta enhances Golgi-localized signaling and is associated with Alzheimer's disease using a recessive mode of inheritance.medRxiv : the preprint server for health sciences · 2025Article
- 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
- Amyloid-β-Driven Synaptic Deficits Are Mediated by Synaptic Removal of GluA3-Containing AMPA Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Cancer-associated mutations in protein kinase C theta are loss-of-function.The Biochemical journal · 2024Article
- Article
- Impaired biogenesis of basic proteins impacts multiple hallmarks of the aging brain.bioRxiv : the preprint server for biology · 2024Article
- PKCα Isoform Inhibits Insulin Signaling and Aggravates Neuronal Insulin Resistance.Molecular neurobiology · 2023Article
- Adipose transplantation improves olfactory function and neurogenesis via PKCα-involved lipid metabolism in Seipin Knockout mice.Stem cell research & therapy · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
- Expression of concern
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a progressive dementia disorder characterized by synaptic degeneration and amyloid-β (Aβ) accumulation in the brain. Through whole-genome sequencing of 1345 individuals from 410 families with late-onset AD (LOAD), we identified three highly penetrant variants in PRKCA, the gene that encodes protein kinase Cα (PKCα), in five of the families. All three variants linked with LOAD displayed increased catalytic activity relative to wild-type PKCα as assessed in live-cell imaging experiments using a genetically encoded PKC activity reporter. Deleting PRKCA in mice or adding PKC antagonists to mouse hippocampal slices infected with a virus expressing the Aβ precursor CT100 revealed that PKCα was required for the reduced synaptic activity caused by Aβ. In PRKCA(-/-) neurons expressing CT100, introduction of PKCα, but not PKCα lacking a PDZ interaction moiety, rescued synaptic depression, suggesting that a scaffolding interaction bringing PKCα to the synapse is required for its mediation of the effects of Aβ. Thus, enhanced PKCα activity may contribute to AD, possibly by mediating the actions of Aβ on synapses. In contrast, reduced PKCα activity is implicated in cancer. Hence, these findings reinforce the importance of maintaining a careful balance in the activity of this enzyme.
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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.