ArticleHuman molecular genetics2015
Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Single molecule array measures of LRRK2 kinase activity in serum link Parkinson's disease severity to peripheral inflammation.Molecular neurodegeneration · 2024Article
- A leucine-rich repeat kinase 2 (LRRK2) pathway biomarker characterization study in patients with Parkinson's disease with and without LRRK2 mutations and healthy controls.Clinical and translational science · 2023Article
- Perspective on the current state of the LRRK2 field.NPJ Parkinson's disease · 2023Review
- Lysosomal Pathogenesis of Parkinson's Disease: Insights From LRRK2 and GBA1 Rodent Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- LRRK2 and Lipid Pathways: Implications for Parkinson's Disease.Biomolecules · 2022Review
- Functional consequence of myeloid ferritin heavy chain on acute and chronic effects of rhabdomyolysis-induced kidney injury.Frontiers in medicine · 2022Article
- Heme Burden and Ensuing Mechanisms That Protect the Kidney: Insights from Bench and Bedside.International journal of molecular sciences · 2021Review
- Parkinson's Disease-Related Genes and Lipid Alteration.International journal of molecular sciences · 2021Review
- UAB-UCSD O'Brien Center for Acute Kidney Injury Research.American journal of physiology. Renal physiology · 2021Review
- LRRK2 Regulates CPT1A to Promote β-Oxidation in HepG2 Cells.Molecules (Basel, Switzerland) · 2020Article
- Progress inFrontiers in neuroscience · 2020Review
- The Emerging Functions of LRRK2 and Rab GTPases in the Endolysosomal System.Frontiers in neuroscience · 2020Review
- Endosomal sorting pathways in the pathogenesis of Parkinson's disease.Progress in brain research · 2020Review
- The Parkinson's disease-linked Leucine-rich repeat kinase 2 (LRRK2) is required for insulin-stimulated translocation of GLUT4.Scientific reports · 2019Article
- The G2019S mutation in LRRK2 imparts resiliency to kinase inhibition.Experimental neurology · 2018Article
- LRRK2 phosphorylates membrane-bound Rabs and is activated by GTP-bound Rab7L1 to promote recruitment to the trans-Golgi network.Human molecular genetics · 2018Article
- A biological network-based regularized artificial neural network model for robust phenotype prediction from gene expression data.BMC bioinformatics · 2017Article
- Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease.Experimental neurology · 2017Review
- Unique sex- and age-dependent effects in protective pathways in acute kidney injury.American journal of physiology. Renal physiology · 2017Article
- Models of LRRK2-Associated Parkinson's Disease.Advances in neurobiology · 2017Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson's disease, and LRRK2 is also linked to Crohn's and Hansen's disease. LRRK2 is expressed in many organs in mammals but is particularly abundant in the kidney. We find that LRRK2 protein is predominantly localized to collecting duct cells in the rat kidney, with much lower expression in other kidney cells. While genetic knockout (KO) of LRRK2 expression is well-tolerated in mice and rats, a unique age-dependent pathology develops in the kidney. The cortex and medulla of LRRK2 KO rat kidneys become darkly pigmented in early adulthood, yet aged animals display no overt signs of kidney failure. Accompanying the dark pigment we find substantial macrophage infiltration in LRRK2 KO kidneys, suggesting the presence of chronic inflammation that may predispose to kidney disease. Unexpectedly, the dark kidneys of the LRRK2 KO rats are highly resistant to rhabdomyolysis-induced acute kidney injury compared with wild-type rats. Biochemical profiling of the LRRK2 KO kidneys using immunohistochemistry, proteomic and lipidomic analyses show a massive accumulation of hemoglobin and lipofuscin in renal tubules that account for the pigmentation. The proximal tubules demonstrate a corresponding up-regulation of the cytoprotective protein heme oxygenase-1 (HO-1) which is capable of mitigating acute kidney injury. The unusual kidney pathology of LRRK2 KO rats highlights several novel physiological roles for LRRK2 and provides indirect evidence for HO-1 expression as a protective mechanism in acute kidney injury in LRRK2 deficiency.
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