ArticleNature communications2022
Enhanced activity of Alzheimer disease-associated variant of protein kinase Cα drives cognitive decline in a mouse model.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Could the cognitive benefits of amyloid-beta clearance grow in time for Alzheimer's disease?Translational psychiatry · 2026Review
- Sex-specific disruptions in PKCγ signaling in a mouse model of spinocerebellar ataxia type 14.JCI insight · 2026Article
- 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
- The antioxidant effect of resveratrol on leukocytes from patients with Alzheimer is independent of SIRT1 signaling pathway.Biochemistry and biophysics reports · 2025Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- PKC-dependent enhancement of glutamate input to VTA dopamine neurons in 3xTg-AD mice.bioRxiv : the preprint server for biology · 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
- A high-performance genetically encoded sensor for cellular imaging of PKC activity in vivo.Nature communications · 2025Article
- A PKCη missense mutation enhances Golgi-localized signaling and is associated with recessively inherited familial Alzheimer's disease.Science signaling · 2025Article
- Photochemical synthesis of natural lipids in artificial and living cells.Nature communications · 2025Article
- Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice.The Journal of clinical investigation · 2025Article
- 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
- Signaling Pathways in Oxidative Stress-Induced Neurodegenerative Diseases: A Review of Phytochemical Therapeutic Interventions.Antioxidants (Basel, Switzerland) · 2025Review
- Sensitive fluorescent biosensor reveals differential subcellular regulation of PKC.Nature chemical biology · 2025Article
- Network pharmacology and metabolomics analysis of Tinospora cordifolia reveals BACE1 and MAOB as potential therapeutic targets for neuroprotection in Alzheimer's disease.Scientific reports · 2025Article
- PKC in the perspective of dopamine receptor signaling.Acta biochimica Polonica · 2025Review
- Astrocytes Lingering at a Crossroads: Neuroprotection and Neurodegeneration in Neurocognitive Dysfunction.International journal of biological sciences · 2025Review
- Fast and deep phosphoproteome analysis with the Orbitrap Astral mass spectrometer.Nature communications · 2024Article
- Cancer-associated mutations in protein kinase C theta are loss-of-function.The Biochemical journal · 2024Article
- Current biomarkers and treatment strategies in Alzheimer disease: An overview and future perspectives.IBRO neuroscience reports · 2024Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Exquisitely tuned activity of protein kinase C (PKC) isozymes is essential to maintaining cellular homeostasis. Whereas loss-of-function mutations are generally associated with cancer, gain-of-function variants in one isozyme, PKCα, are associated with Alzheimer's disease (AD). Here we show that the enhanced activity of one variant, PKCα M489V, is sufficient to rewire the brain phosphoproteome, drive synaptic degeneration, and impair cognition in a mouse model. This variant causes a modest 30% increase in catalytic activity without altering on/off activation dynamics or stability, underscoring that enhanced catalytic activity is sufficient to drive the biochemical, cellular, and ultimately cognitive effects observed. Analysis of hippocampal neurons from PKCα M489V mice reveals enhanced amyloid-β-induced synaptic depression and reduced spine density compared to wild-type mice. Behavioral studies reveal that this mutation alone is sufficient to impair cognition, and, when coupled to a mouse model of AD, further accelerates cognitive decline. The druggability of protein kinases positions PKCα as a promising therapeutic target in AD.
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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 Socratic graph.