ArticleAging cell2019
PKR knockout in the 5xFAD model of Alzheimer's disease reveals beneficial effects on spatial memory and brain lesions.
Article in Aging cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 43 citations in OpenAlex.
- Distinct cell type-specific mechanisms underlie cognitive dysfunction during persistent integrated stress response activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- RNA imbalance as a hallmark of cellular ageing.Nature cell biology · 2026Review
- Circular RNA aptamers targeting neuroinflammation ameliorate Alzheimer disease phenotypes in mouse models.Nature biotechnology · 2026Article
- Monoclonal antibodies and small molecules: on the cutting edge of Alzheimer's disease therapy.Frontiers in cell and developmental biology · 2026Review
- From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape.Medicina (Kaunas, Lithuania) · 2025Review
- Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review.Molecular biology reports · 2025Review
- Astrocytes, via RTP801, contribute to cognitive decline by disrupting GABAergic-regulated connectivity and driving neuroinflammation in an Alzheimer's disease mouse model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion.Neuron · 2025Article
- RNA dysregulation in neurodegenerative diseases.The EMBO journal · 2025Review
- The integrated stress response in brain diseases: A double-edged sword for proteostasis and synapses.Current opinion in neurobiology · 2024Review
- The Sixth Sense: Self-nucleic acid sensing in the brain.Advances in immunology · 2024Review
- Disrupted Maturation of Prefrontal Layer 5 Neuronal Circuits in an Alzheimer's Mouse Model of Amyloid Deposition.Neuroscience bulletin · 2023Article
- Role of the caspase-8/RIPK3 axis in Alzheimer's disease pathogenesis and Aβ-induced NLRP3 inflammasome activation.JCI insight · 2023Article
- Transcriptome analysis reveals genes associated with stem cell activation by physical exercise in the dentate gyrus of aged p16Ink4a knockout mice.Frontiers in cell and developmental biology · 2023Article
- Cerebrospinal Fluid Alpha-Synuclein Improves the Differentiation between Dementia with Lewy Bodies and Alzheimer's Disease in Clinical Practice.International journal of molecular sciences · 2022Article
- The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer's disease.Neurobiology of disease · 2022Article
- eIF2-dependent translation initiation: Memory consolidation and disruption in Alzheimer's disease.Seminars in cell & developmental biology · 2022Review
- Brain-wide Cas9-mediated cleavage of a gene causing familial Alzheimer's disease alleviates amyloid-related pathologies in mice.Nature biomedical engineering · 2022Article
- Neddylation-dependent protein degradation is a nexus between synaptic insulin resistance, neuroinflammation and Alzheimer's disease.Translational neurodegeneration · 2022Article
- The role of PKC/PKR in aging, Alzheimer's disease, and perioperative neurocognitive disorders.Frontiers in aging neuroscience · 2022Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
Brain lesions in Alzheimer's disease (AD) include amyloid plaques made of Aβ peptides and neurofibrillary tangles composed of hyperphosphorylated tau protein with synaptic and neuronal loss and neuroinflammation. Aβ oligomers can trigger tau phosphorylation and neuronal alterations through activation of neuronal kinases leading to progressive cognitive decline. PKR is a ubiquitous pro-apoptotic serine/threonine kinase, and levels of activated PKR are increased in AD brains and AD CSF. In addition, PKR regulates negatively memory formation in mice. To assess the role of PKR in an AD in vivo model, we crossed 5xFAD transgenic mice with PKR knockout (PKRKO) mice and we explored the contribution of PKR on cognition and brain lesions in the 5xFAD mouse model of AD as well as in neuron-microglia co-cultures exposed to the innate immunity activator lipopolysaccharide (LPS). Nine-month-old double-mutant mice revealed significantly improved memory consolidation with the new object location test, starmaze test, and elevated plus maze test as compared to 5xFAD mice. Brain amyloid accumulation and BACE1 levels were statistically decreased in double-mutant mice. Apoptosis, neurodegeneration markers, and synaptic alterations were significantly reduced in double-mutant mice as well as neuroinflammation markers such as microglial load and brain cytokine levels. Using cocultures, we found that PKR in neurons was essential for LPS microglia-induced neuronal death. Our results demonstrate the clear involvement of PKR in abnormal spatial memory and brain lesions in the 5xFAD model and underline its interest as a target for neuroprotection 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 OpenQuestion graph.