ArticleThe EMBO journal2022
Unfolded protein response IRE1/XBP1 signaling is required for healthy mammalian brain aging.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 68 citations in OpenAlex.
- Metformin alleviates aging-associated periodontitis via NRF2-mediated restoration of the IRE1α dependent unfolded protein response.Bioactive materials · 2026Article
- Dual IRE1 targets: Determinants of the cell fate?The FEBS journal · 2026Review
- Aging-Related Changes in the Injury Response of the Peripheral Nervous System.Neuroscience bulletin · 2026Review
- Proteostasis decline and endoplasmic reticulum stress in aging: Implications for cellular senescence and senescence-associated secretory phenotype regulation.Neural regeneration research · 2026Article
- Photo- and Immunotherapy Interface: Can Dendritic Cell Vaccines Overcome the Limitations of PDT?Pharmaceutics · 2026Review
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- Adaptive inter-tissue proteostasis networks in aging and neurodegeneration.Bioscience reports · 2026Review
- X-Box Binding Protein 1 Regulates Osteogenesis of Periodontal Ligament Cells During Aging by Modulating P53 Signaling Pathway.Stem cells international · 2026Article
- Developmentally-regulated post-apocrine cell death ofFrontiers in cell and developmental biology · 2026Article
- Adaptive-to-maladaptive IRE1α signaling as a driver of amyloidogenic APP processing in Alzheimer's disease.Frontiers in molecular biosciences · 2026Review
- HSPA12B Protects Against Age-Related Endothelial Cell Senescence by Regulating STING Degradation.Aging cell · 2025Article
- K29-Linked Ubiquitination of Transcription Regulators Controls Cell Proliferation in the Unfolded Protein Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Exerkine irisin mitigates cognitive impairment by suppressing gut-brain axis-mediated inflammation.Journal of advanced research · 2025Article
- Neurons whisper, tissues respond: neurons as orchestrators of stress responses.Nature reviews. Molecular cell biology · 2025Article
- Development of an Adaptive, Economical, and Easy-to-Use SP3-TMT Automated Sample Preparation Workflow for Quantitative Proteomics.Journal of proteome research · 2025Article
- ADNP is essential for sex-dependent hippocampal neurogenesis, through male unfolded protein response and female mitochondrial gene regulation.Molecular psychiatry · 2025Article
- Single-cell RNA-seq analysis reveals the multi-step process of cellular senescence.Biochemistry and biophysics reports · 2025Article
- The protective role of the IRE1α/XBP1 signaling cascade in autophagy during ischemic stress and acute kidney injury.Cell stress & chaperones · 2025Article
Corrections and comments
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Authors and funding
29 authors at 9 institutions in 4 countries.
Funding
Abstract
Aging is a major risk factor to develop neurodegenerative diseases and is associated with decreased buffering capacity of the proteostasis network. We investigated the significance of the unfolded protein response (UPR), a major signaling pathway activated to cope with endoplasmic reticulum (ER) stress, in the functional deterioration of the mammalian brain during aging. We report that genetic disruption of the ER stress sensor IRE1 accelerated age-related cognitive decline. In mouse models, overexpressing an active form of the UPR transcription factor XBP1 restored synaptic and cognitive function, in addition to reducing cell senescence. Proteomic profiling of hippocampal tissue showed that XBP1 expression significantly restore changes associated with aging, including factors involved in synaptic function and pathways linked to neurodegenerative diseases. The genes modified by XBP1 in the aged hippocampus where also altered. Collectively, our results demonstrate that strategies to manipulate the UPR in mammals may help sustain healthy brain aging.
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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.