ArticleCell death & disease2018
Brain injury induces HIF-1α-dependent transcriptional activation of LRRK2 that exacerbates brain damage.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 52 citations in OpenAlex.
- Clinical associations during the year before Parkinson's disease diagnosis in Taiwan: a nationwide claims-based case-control study.Annals of medicine · 2026Article
- Therapeutic Effect of Alpha-Pinene on In Vitro and In Vivo Models of Mild Traumatic Brain Injury.Life (Basel, Switzerland) · 2026Article
- Targeting Peptidylarginine Deiminases in Neurons and Astrocytes in Central Nervous System Injury-Effects of Pan-PAD Inhibitor Cl-Amidine in an Oxygen-Glucose Deprivation Model of Ischaemia (OGD/R) and LPS Stimulation In Vitro.International journal of molecular sciences · 2026Article
- Extracellular matrix remodelling in neurological diseases.Nature reviews. Neurology · 2026Review
- Hypoxia-inducible factor-1α: Dual roles in maintaining neuronal homeostasis and neuronal degeneration via regulation of oxidative stress, mitochondrial dynamics, and bioenergetics.Journal of physiology and biochemistry · 2026Review
- Potential Protective Effects of Naloxone in Traumatic Brain Injury Through JAK2/STAT3 Signaling Modulation.Life (Basel, Switzerland) · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- Targeting leucine-rich repeat kinase 2 overcomes resistance to oncolytic herpes simplex virus-based therapies in glioblastoma.Nature communications · 2026Article
- Amantadine Attenuates Secondary Oxidative and Inflammatory Injury by Modulating the HIF-1α/BNIP3L/HMGB1 Axis in Rat Model of Traumatic Brain Injury.Medicina (Kaunas, Lithuania) · 2026Article
- Mechanical compression induces neuronal apoptosis, reduces synaptic activity, and promotes glial neuroinflammation in mice and humans.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Benzoate Drugs for Traumatic Brain Injury.Journal of clinical & experimental immunology · 2026Article
- Carvacrol improves neurological function by inhibiting TRPM7-mediated BBB disruption and hemorrhage after TBI.Acta neuropathologica communications · 2025Article
- Hydrogen Gas Mitigates Acute Hypoxia-Induced Oxidative and Inflammatory Brain Injuries in Medaka (Antioxidants (Basel, Switzerland) · 2025Article
- A Common Mutation in the Homeostatic Iron Regulatory Gene Alters Astrocyte Migration and Redox Profile.FASEB bioAdvances · 2025Article
- Zipper-interacting protein kinase mediates neuronal cell death and cognitive dysfunction in traumatic brain injury via regulating DEDD.Cell death & disease · 2025Article
- Hypoxia Pathways in Parkinson's Disease: From Pathogenesis to Therapeutic Targets.International journal of molecular sciences · 2024Review
- Therapeutic Effect of Donepezil on Neuroinflammation and Cognitive Impairment after Moderate Traumatic Brain Injury.Life (Basel, Switzerland) · 2024Article
- Pharmacological Inhibition of LRRK2 Exhibits Neuroprotective Activity in Mouse Photothrombotic Stroke Model.Experimental neurobiology · 2024Article
- Controlled Decompression Alleviates Motor Dysfunction by Regulating Microglial Polarization via the HIF-1α Signaling Pathway in Intracranial Hypertension.Molecular neurobiology · 2023Article
- Oxiracetam alleviates anti-inflammatory activity and ameliorates cognitive impairment in the early phase of traumatic brain injury.Acta neurochirurgica · 2023Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leucine-rich repeat kinase 2 (LRRK2), originally identified as a causative genetic factor in Parkinson's disease, is now associated with a number of pathologies. Here, we show that brain injury induces a robust expression of endogenous LRRK2 and suggest a role of LRRK2 after injury. We found that various in vitro and in vivo models of traumatic brain injury (TBI) markedly enhanced LRRK2 expression in neurons and also increased the level of hypoxia-inducible factor (HIF)-1α. Luciferase reporter assay and chromatin immunoprecipitation revealed direct binding of HIF-1α in LRRK2 proximal promoter. We also found that HIF-1α-dependent transcriptional induction of LRRK2 exacerbated neuronal cell death following injury. Furthermore, application of G1023, a specific, brain-permeable inhibitor of LRRK2, substantially prevented brain tissue damage, cell death, and inflammatory response and alleviated motor and cognitive defects induced by controlled cortical impact injury. Together, these results suggest HIF-1α-LRRK2 axis as a potential therapeutic target for brain injury.
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