ArticleLaboratory investigation; a journal of technical methods and pathology2011
A novel origin for granulovacuolar degeneration in aging and Alzheimer's disease: parallels to stress granules.
Article in Laboratory investigation; a journal of technical methods and pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 45 citations in OpenAlex.
- Hearing modulation affects Alzheimer's disease progression linked to brain inflammation: a study in mouse models.Molecular medicine (Cambridge, Mass.) · 2024Article
- Extracellular Vesicles, Cell-Penetrating Peptides and miRNAs as Future Novel Therapeutic Interventions for Parkinson's and Alzheimer's Disease.Biomedicines · 2023Review
- Intraneuronal sortilin aggregation relative to granulovacuolar degeneration, tau pathogenesis and sorfra plaque formation in human hippocampal formation.Frontiers in aging neuroscience · 2022Article
- Response to stress in biological disorders: Implications of stress granule assembly and function.Cell proliferation · 2021Review
- Stress Granules and Neurodegenerative Disorders: A Scoping Review.Frontiers in aging neuroscience · 2021Article
- The Significance of Tau Aggregates in the Human Brain.Brain sciences · 2020Review
- Mitophagy alterations in Alzheimer's disease are associated with granulovacuolar degeneration and early tau pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2020Article
- Novel mTORC1 Mechanism Suggests Therapeutic Targets for COMPopathies.The American journal of pathology · 2019Article
- Chronically stressed or stress-preconditioned neurons fail to maintain stress granule assembly.Cell death & disease · 2017Article
- Mitochondrial dysfunction and oxidative stress in aging and cancer.Oncotarget · 2016Review
- Granulovacuolar Degeneration in Hippocampus of Neurodegenerative Diseases: Quantitative Study.Journal of neurodegenerative diseases · 2016Article
- Re-examining tau-immunoreactive pathology in the population: granulovacuolar degeneration and neurofibrillary tangles.Alzheimer's research & therapy · 2015Article
- Stress granule-defective mutants deregulate stress responsive transcripts.PLoS genetics · 2014Article
- miRNAs at the interface of cellular stress and disease.The EMBO journal · 2014Review
- Phosphatidylinositol-4,5-bisphosphate is enriched in granulovacuolar degeneration bodies and neurofibrillary tangles.Neuropathology and applied neurobiology · 2014Article
- Antimicrobial peptide β-defensin-1 expression is upregulated in Alzheimer's brain.Journal of neuroinflammation · 2013Article
- 8-hydroxy-2'-deoxyguanosine in colorectal adenocarcinoma--is it a result of oxidative stress?Medical science monitor : international medical journal of experimental and clinical research · 2013Article
- TDP-43 aggregation in neurodegeneration: are stress granules the key?Brain research · 2012Review
- The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons.Journal of neuropathology and experimental neurology · 2012Article
- Hydroxynonenal-generated crosslinking fluorophore accumulation in Alzheimer disease reveals a dichotomy of protein turnover.Free radical biology & medicine · 2012Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
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Abstract
The phosphorylated ribosomal protein S6 (pS6) is associated with the 40S ribosomal subunit in eukaryotes and is thought to have a role in RNA storage, degradation, and re-entry into translation. In this study, we found pS6 localized to granulovacuolar degeneration (GVD) within the pyramidal neurons. Immunohistochemical analysis found that nearly 20-fold more neurons contain pS6-positive granules in Alzheimer's disease (AD) hippocampus compared with age-matched controls. Further, pS6-positive granules were more common in neurons not containing neurofibrillary tangles (NFTs), were never associated with extracellular NFTs or in apoptotic neurons, and contained less RNA than neighboring pyramidal neurons not containing pS6-positive granules. In model systems, pS6 is a specific marker for stress granules, and another stress granule protein, p54/Rck, was also found to be a component of GVD in the current study. Stress granules are transient, intracellular, dense aggregations of proteins and RNAs that accumulate as a stress response, protecting cells from apoptosis and inappropriate transcriptional activity, often described as a form of 'molecular triage.' The RNA oxidation modification 8-hydroxyguanosine (8OHG) is strikingly increased in AD, yet this study reports that those neurons with pS6 granules display reduced RNA oxidation demonstrated by lower levels of 8OHG. Since chronic oxidative stress is central to AD pathogenesis, and RNA is a specific oxidative stress target and is intimately associated with stress granule biogenesis in model systems, we suggest that GVD in human brain parallel stress granules, and may in fact be more representative of early disease pathogenesis than traditionally believed. This proposed origin for GVD as a neuroprotective response, may represent a morphologic checkpoint between cell death and reversible cellular stress that proceeds in the absence of other inclusions.
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