ArticleFrontiers in cellular neuroscience2018
LRRK2 Contributes to Secondary Brain Injury Through a p38/Drosha Signaling Pathway After Traumatic Brain Injury in Rats.
Article in Frontiers in cellular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Traumatic MicroRNAs: Deconvolving the Signal After Severe Traumatic Brain Injury.Cellular and molecular neurobiology · 2023Pooled it
- LRRK2 kinase activity restricts NRF2-dependent mitochondrial protection in microglia.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- RACK1 promotes autophagy via the PERK signaling pathway to protect against traumatic brain injury in rats.CNS neuroscience & therapeutics · 2024Article
- Infectious Diseases.Advances in neurobiology · 2024Review
- Inhibition of LRRK2 Attenuates Depression-Related Symptoms in Mice with Moderate Traumatic Brain Injury.Cells · 2023Article
- Upregulation of LRRK2 following traumatic brain injury does not directly phosphorylate ThrFrontiers in cellular neuroscience · 2023Article
- LRRK2 Inhibition by PF06447475 Antagonist Modulates Early Neuronal Damage after Spinal Cord Trauma.Antioxidants (Basel, Switzerland) · 2022Article
- Microglia and Neuroinflammation: Crucial Pathological Mechanisms in Traumatic Brain Injury-Induced Neurodegeneration.Frontiers in aging neuroscience · 2022Review
- Inhibition of PDE10A-Rescued TBI-Induced Neuroinflammation and Apoptosis through the cAMP/PKA/NLRP3 Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The pivotal role of the NLRC4 inflammasome in neuroinflammation after intracerebral hemorrhage in rats.Experimental & molecular medicine · 2021Article
- Targeting autophagy using small-molecule compounds to improve potential therapy of Parkinson's disease.Acta pharmaceutica Sinica. B · 2021Review
- Inhibition of LRRK2-Rab10 Pathway Improves Secondary Brain Injury After Surgical Brain Injury in Rats.Frontiers in surgery · 2021Article
- LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case-control association study for Parkinson's disease.Molecular genetics & genomic medicine · 2019Article
- Potential Roles of NIX/BNIP3L Pathway in Rat Traumatic Brain Injury.Cell transplantation · 2019Article
- 2-BFI Provides Neuroprotection Against Inflammation and Necroptosis in a Rat Model of Traumatic Brain Injury.Frontiers in neuroscience · 2019Article
- Brain injury induces HIF-1α-dependent transcriptional activation of LRRK2 that exacerbates brain damage.Cell death & disease · 2018Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leucine-rich repeat kinase 2 (LRRK2) is widely expressed in the brain and exerts neurotoxicity in Parkinson's disease. The p38/Drosha signaling activation has been reported to increase cell death under stress. This study was designed to investigate the potential role and mechanism of LRRK2 in secondary brain injury after traumatic brain injury (TBI). A total of 130 male Sprague-Dawley rats were examined using a weight-drop model of TBI. The rats received the specific LRRK2 inhibitor PF-06447475 or LRRK2 pDNA alone or in combination with Drosha pDNA. Real-time PCR, western blot, immunofluorescence, neuronal apoptosis, brain water content, and neurological score analyses were conducted. Our results showed that after TBI, endogenous LRRK2 expression and p38 phosphorylation were increased, whereas Drosha expression was inhibited. Administration of the LRRK2 inhibitor PF-06447475 significantly reduced neuronal apoptosis, brain water content, and blood-brain barrier permeability 12 h after TBI and ameliorated neurological deficits 72 h after TBI, which was concomitant with decreased p38 phosphorylation and increased Drosha expression. Conversely, LRRK2 overexpression induced the opposite effect. Moreover, the neurotoxic effects of LRRK2 on TBI were also eliminated by Drosha overexpression. Altogether, these findings demonstrate the importance of TBI-induced LRRK2 upregulation during the induction of post-traumatic neurological injury, which may be partially mediated through a p38/Drosha signaling pathway.
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