ArticleiScience2022
Histone H2A ubiquitination resulting from Brap loss of function connects multiple aging hallmarks and accelerates neurodegeneration.
Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Epigenetic Modulation Is a Key Mechanism in Cognitive Deficit: Unveiling Garcinol as a Potent HAT Inhibitor in Improving Alzheimer's Disease.ACS omega · 2026Review
- Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling.bioRxiv : the preprint server for biology · 2026Article
- Review
- Boosting Brain Clean-Up: Can Targeting UPS Genes Offer Neuroprotection?Molecular neurobiology · 2025Review
- Ubiquitin-Proteasome System Dysregulation in Alzheimer's Disease Impacts Protein Abundance.bioRxiv : the preprint server for biology · 2025Article
- BRAP Promotes the Tumorigenesis of Hepatocellular Carcinoma by Corrupting Cancer Cell Cycle Regulation and Enhancing Immune Evasion.Journal of hepatocellular carcinoma · 2025Article
- PPIA-coExp: Discovering Context-Specific Biomarkers Based on Protein-Protein Interactions, Co-Expression Networks, and Expression Data.International journal of molecular sciences · 2024Article
- Genetic and Epigenetic Interactions Involved in Senescence of Stem Cells.International journal of molecular sciences · 2024Review
- Review
- An Overview of the Epigenetic Modifications in the Brain under Normal and Pathological Conditions.International journal of molecular sciences · 2024Review
- Genomic Instability and Epigenetic Changes during Aging.International journal of molecular sciences · 2023Review
- Nde1 is required for heterochromatin compaction and stability in neocortical neurons.iScience · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Aging is an intricate process characterized by multiple hallmarks including stem cell exhaustion, genome instability, epigenome alteration, impaired proteostasis, and cellular senescence. Whereas each of these traits is detrimental at the cellular level, it remains unclear how they are interconnected to cause systemic organ deterioration. Here we show that abrogating Brap, a BRCA1-associated protein essential for neurogenesis, results in persistent DNA double-strand breaks and elevation of histone H2A mono- and poly-ubiquitination (H2Aub). These defects extend to cellular senescence and proteasome-mediated histone H2A proteolysis with alterations in cells' proteomic and epigenetic states. Brap deletion in the mouse brain causes neuroinflammation, impaired proteostasis, accelerated neurodegeneration, and substantially shortened the lifespan. We further show the elevation of H2Aub also occurs in human brain tissues with Alzheimer's disease. These data together suggest that chromatin aberrations mediated by H2Aub may act as a nexus of multiple aging hallmarks and promote tissue-wide degeneration.
Indexed as
Identifiers
What OpenQuestion holds
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.