ArticleCell death & disease2019
IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson's disease.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- Article
- Endoplasmic Reticulum Stress-Induced Endothelial Cell Pyroptosis Contributes to Pulmonary Vascular Remodeling and Pulmonary Arterial Hypertension via IRE1α/Caspase-3/GSDME Pathway.Journal of the American Heart Association · 2026Article
- Discovery of a pyrazolopyridine alkaloid that mitigates neuronal ER stress and age-related decline.Communications biology · 2026Article
- TMBIM6 enhances dopaminergic neuron survival by modulating the IRE1a pathway in Parkinson's disease.Cell death & disease · 2026Article
- Staphylococcus aureus-induced degeneration of nociceptive neurons in Caenorhabditis elegans.BMC biology · 2025Article
- The cell autonomous and non-autonomous functions of Rab27 in longevity and neuroprotection inAutophagy · 2025Article
- 18β-Glycyrrhetinic Acid Regulates Endoplasmic Reticulum Stress and Autophagy Dysregulation in the MPTP/p-Induced Model of Parkinson Disease.Molecular neurobiology · 2025Article
- A novel role for the E2F transcription factor and the ER stress sensor IRE1 in cytoplasmic DNA accumulation.Genetics · 2025Article
- K29-Linked Ubiquitination of Transcription Regulators Controls Cell Proliferation in the Unfolded Protein Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- miRNAs in neurodegenerative diseases: from target screening to precision therapy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- ER stress sensors at the ER-mitochondrial interface, controlling mitochondrial health in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Article
- Endothelial Unfolded Protein Response-Mediated Cytoskeletal Effects.Cell biochemistry and function · 2024Review
- Lauric acid with or without levodopa ameliorates Parkinsonism in genetically modified model of Drosophila melanogaster via the oxidative-inflammatory-apoptotic pathway.Brain and behavior · 2024Article
- IRE1/JNK Is the Leading UPR Pathway in 6-OHDA-Induced Degeneration of Differentiated SH-SY5Y Cells.International journal of molecular sciences · 2024Article
- Role of Inositol-Requiring Enzyme 1 and Autophagy in the Pro-Fibrotic Mechanism Underlying Graves' Orbitopathy.Yonsei medical journal · 2024Article
- Modeling neurodegenerative and neurodevelopmental disorders in theLearning & memory (Cold Spring Harbor, N.Y.) · 2024Review
- Autophagy-associated non-coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis.CNS neuroscience & therapeutics · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal aggregation of misfolded pathological proteins in neurons is a prominent feature of neurodegenerative disorders including Parkinson's disease (PD). Perturbations of proteostasis at the endoplasmic reticulum (ER) triggers ER stress, activating the unfolded protein response (UPR). Chronic ER stress is thought to underlie the death of neurons during the neurodegenerative progression, but the precise mechanism by which the UPR pathways regulate neuronal cell fate remains incompletely understood. Here we report a critical neurodegenerative role for inositol-requiring enzyme 1 (IRE1), the evolutionarily conserved ER stress sensor, in a Drosophila model of PD. We found that IRE1 was hyperactivated upon accumulation of α-synuclein in the fly photoreceptor neurons. Ectopic overexpression of IRE1 was sufficient to trigger autophagy-dependent neuron death in an XBP1-independent, JNK-dependent manner. Furthermore, IRE1 was able to promote dopaminergic neuron loss, progressive locomotor impairment, and shorter lifespan, whereas blocking IRE1 or ATG7 expression remarkably ameliorated the progression of α-synuclein-caused Parkinson's disease. These results provide in vivo evidence demonstrating that the IRE1 pathway drives PD progression through coupling ER stress to autophagy-dependent neuron death.
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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.