ArticleNeuron2016
Activation of HIPK2 Promotes ER Stress-Mediated Neurodegeneration in Amyotrophic Lateral Sclerosis.
Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00821132 (Identification of Genes Causing Familial ALS or Increasing Risk for Sporadic ALS and ALS With Frontotemporal Dementia and Understanding Disease Mechanism.), which is not on this map. Cited by 52 papers.
What it found
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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.
Identification of Genes Causing Familial ALS or Increasing Risk for Sporadic ALS and ALS With Frontotemporal Dementia and Understanding Disease Mechanism.
Who cites it
52 citing papers in PubMed, 84 citations in OpenAlex.
- Flunarizine changes microRNA expression in cell cultures and in a mouse model of spinal muscular atrophy.Scientific reports · 2026Article
- Pridopidine Protects ALS Patient-Derived Neural Progenitor Cells via Sigma-1 Receptor Activation.International journal of molecular sciences · 2026Article
- Ubiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Circular RNA expression in ALS is progressively deregulated and tissue-dependent.BMC genomics · 2025Article
- Paired blood and brain tissue methylation biomarkers in focal cortical dysplasia.Brain communications · 2025Article
- The Neuroprotective Effect of the X Protein of Orthobornavirus Bornaense Type 1 in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2024Article
- Understanding the Role of the SMN Complex Component GEMIN5 and Its Functional Relationship with Demethylase KDM6B in the Flunarizine-Mediated Neuroprotection of Motor Neuron Disease Spinal Muscular Atrophy.International journal of molecular sciences · 2024Article
- Doxycycline for transgene control disrupts gut microbiome diversity without compromising acute neuroinflammatory response.Journal of neuroinflammation · 2024Article
- Dual roles of UPRJournal of molecular medicine (Berlin, Germany) · 2023Review
- Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.FEBS letters · 2023Review
- Article
- HIPK2 in the physiology of nervous system and its implications in neurological disorders.Biochimica et biophysica acta. Molecular cell research · 2023Review
- PolyGA targets the ER stress-adaptive response by impairing GRP75 function at the MAM in C9ORF72-ALS/FTD.Acta neuropathologica · 2022Article
- Sevoflurane-Induced Neurotoxicity in the Developing Hippocampus via HIPK2/AKT/mTOR Signaling.Neurotoxicity research · 2022Article
- HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- MicroRNA-8126-Mediated Antioxidant Stress Attenuates Isoflurane-Induced Hippocampal Neurotoxicity in Developing Rats.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Mitogen-Activated Protein Kinase Pathway in Amyotrophic Lateral Sclerosis.Biomedicines · 2021Review
- CircRNA-016901 silencing attenuates irradiation-induced injury in bone mesenchymal stem cells via regulating the miR-1249-5p/HIPK2 axis.Experimental and therapeutic medicine · 2021Article
- Amide signal intensities may be reduced in the motor cortex and the corticospinal tract of ALS patients.European radiology · 2021Article
- Disruption of Endoplasmic Reticulum Proteostasis in Age-Related Nervous System Disorders.Progress in molecular and subcellular biology · 2021Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Persistent accumulation of misfolded proteins causes endoplasmic reticulum (ER) stress, a prominent feature in many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Here we report the identification of homeodomain interacting protein kinase 2 (HIPK2) as the essential link that promotes ER-stress-induced cell death via the IRE1α-ASK1-JNK pathway. ER stress, induced by tunicamycin or SOD1(G93A), activates HIPK2 by phosphorylating highly conserved serine and threonine residues (S359/T360) within the activation loop of the HIPK2 kinase domain. In SOD1(G93A) mice, loss of HIPK2 delays disease onset, reduces cell death in spinal motor neurons, mitigates glial pathology, and improves survival. Remarkably, HIPK2 activation positively correlates with TDP-43 proteinopathy in NEFH-tTA/tetO-hTDP-43ΔNLS mice, sporadic ALS and C9ORF72 ALS, and blocking HIPK2 kinase activity protects motor neurons from TDP-43 cytotoxicity. These results reveal a previously unrecognized role of HIPK2 activation in ER-stress-mediated neurodegeneration and its potential role as a biomarker and therapeutic target for ALS. VIDEO ABSTRACT.
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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.