ArticleMolecular psychiatry2021
Dysregulation of the unfolded protein response (UPR) in the dorsolateral prefrontal cortex in elderly patients with schizophrenia.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Dissecting Schizophrenia Biology Using Pleiotropy With Cognitive Genomics.Biological psychiatry · 2025Pooled it
- Transcription-protein dissociation reveals disrupted cellular stress pathways in the prefrontal cortex of depression and schizophrenia subjects.Molecular biomedicine · 2026Article
- Heavy metal toxicity as a driver of endoplasmic reticulum stress and dysfunction.The FEBS journal · 2026Review
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- Premature aging in serious mental illness.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Distinct microRNA profiles in neuron-derived extracellular vesicles between recent-onset and chronic-phase schizophrenia.Schizophrenia (Heidelberg, Germany) · 2025Article
- Molecular Underpinning of Treatment-Resistant Schizophrenia: A Putative Different Neurobiology from Treatment-Responsive Schizophrenia.International journal of molecular sciences · 2025Review
- ADNP is essential for sex-dependent hippocampal neurogenesis, through male unfolded protein response and female mitochondrial gene regulation.Molecular psychiatry · 2025Article
- Ultrastructural disturbances in microglia-neuron interactions in the head of the caudate nucleus in schizophrenia.European archives of psychiatry and clinical neuroscience · 2025Article
- Single-Cell Transcriptional Profiling Reveals Cell Type-Specific Sex-Dependent Molecular Patterns of Schizophrenia.International journal of molecular sciences · 2025Article
- ER stress sensors at the ER-mitochondrial interface, controlling mitochondrial health in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- The neuropathobiology of multiple sclerosis.Nature reviews. Neuroscience · 2024Review
- ER stress in mouse serotonin neurons triggers a depressive phenotype alleviated by ketamine targeting eIF2α signaling.iScience · 2024Article
- Dissecting Schizophrenia Biology Using Pleiotropy with Cognitive Genomics.medRxiv : the preprint server for health sciences · 2024Article
- Understanding the Unfolded Protein Response (UPR) Pathway: Insights into Neuropsychiatric Disorders and Therapeutic Potentials.Biomolecules & therapeutics · 2024Review
- Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures.Translational psychiatry · 2024Article
- Central insulin dysregulation in antipsychotic-naïve first-episode psychosis: In silico exploration of gene expression signatures.Psychiatry research · 2024Article
- Aberrant glycosylation in schizophrenia: insights into pathophysiological mechanisms and therapeutic potentials.Frontiers in pharmacology · 2024Review
- Basic research and opportunities for translational advancement in the field of mammalian ∼12-hour ultradian chronobiology.Frontiers in physiology · 2024Review
- Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice.PloS one · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Abnormalities in protein localization, function, and posttranslational modifications are targets of schizophrenia (SCZ) research. As a major contributor to the synthesis, folding, trafficking, and modification of proteins, the endoplasmic reticulum (ER) is well-positioned to sense cellular stress. The unfolded protein response (UPR) is an evolutionarily conserved adaptive reaction to environmental and pathological perturbation in ER function. The UPR is a highly orchestrated and complex cellular response, which is mediated through the ER chaperone protein, BiP, three known ER transmembrane stress sensors, protein kinase RNA-like ER kinase (PERK), activating transcription factor-6 (ATF6), inositol requiring enzyme 1α (IRE1α), and their downstream effectors. In this study, we measured protein expression and phosphorylation states of UPR sensor pathway proteins in the dorsolateral prefrontal cortex (DLPFC) of 22 matched pairs of elderly SCZ and comparison subjects. We observed increased protein expression of BiP, decreased PERK, and decreased phosphorylation of IRE1α. We also observed decreased p-JNK2 and increased sXBP1, downstream targets of the IRE1α arm of the UPR. The disconnect between decreased p-IRE1α and increased sXBP1 protein expression led us to measure sXbp1 mRNA. We observed increased expression of the ratio of sXbp1/uXbp1 transcripts, suggesting that splicing of Xbp1 mRNA by IRE1α is increased and drives upregulation of sXBP1 protein expression. These findings suggest an abnormal pattern of UPR activity in SCZ, with specific dysregulation of the IRE1α arm. Dysfunction of this system may lead to abnormal responses to cellular stressors and contribute to protein processing abnormalities previously observed in SCZ.
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Registered trials
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