ArticleHuman molecular genetics2018
Proteomic analysis reveals co-ordinated alterations in protein synthesis and degradation pathways in LRRK2 knockout mice.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
- Generation of Leucine-Rich Repeat Kinase 2 (LRRK2) Knockout Neuroblastoma Cells SH-SY5Y by CRISPR/Cas9-Mediated Genome Editing.Biochemical genetics · 2026Article
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- Experimental Models and Translational Strategies in Neuroprotective Drug Development with Emphasis on Alzheimer's Disease.Molecules (Basel, Switzerland) · 2026Review
- Tau uptake by human neurons depends on receptor LRP1 and kinase LRRK2.The EMBO journal · 2025Article
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- Mechanisms of lysosomal tubulation and sorting driven by LRRK2.Biochemical Society transactions · 2024Review
- Role of the Insulin-like Growth Factor System in Neurodegenerative Disease.International journal of molecular sciences · 2024Review
- G2019S selective LRRK2 kinase inhibitor abrogates mitochondrial DNA damage.NPJ Parkinson's disease · 2024Article
- Single-nuclei RNA sequencing uncovers heterogenous transcriptional signatures in Parkinson's disease associated with nuclear receptor-related factor 1 defect.Neural regeneration research · 2023Article
- LRRK2 suppresses lysosome degradative activity in macrophages and microglia through MiT-TFE transcription factor inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- LRRK2 phosphorylation status and kinase activity regulate (macro)autophagy in a Rab8a/Rab10-dependent manner.Cell death & disease · 2023Article
- Role of rodent models in advancing precision medicine for Parkinson's disease.Handbook of clinical neurology · 2023Review
- LRRK2 recruitment, activity, and function in organelles.The FEBS journal · 2022Review
- Inflammation and immune dysfunction in Parkinson disease.Nature reviews. Immunology · 2022Review
- Lysosomal positioning regulates Rab10 phosphorylation at LRRK2Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson's disease.NPJ Parkinson's disease · 2022Article
- Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease.Cell reports. Medicine · 2022Article
- LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease.Translational neurodegeneration · 2022Review
- Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease.Annals of neurology · 2021Article
- Genes Implicated in Familial Parkinson's Disease Provide a Dual Picture of Nigral Dopaminergic Neurodegeneration with Mitochondria Taking Center Stage.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Mutations in leucine-rich repeat kinase 2 (LRRK2) segregate with familial Parkinson's disease (PD) and genetic variation around LRRK2 contributes to risk of sporadic disease. Although knockout (KO) of Lrrk2 or knock-in of pathogenic mutations into the mouse germline does not result in a PD phenotype, several defects have been reported in the kidneys of Lrrk2 KO mice. To understand LRRK2 function in vivo, we used an unbiased approach to determine which protein pathways are affected in LRRK2 KO kidneys. We nominated changes in cytoskeletal-associated proteins, lysosomal proteases, proteins involved in vesicular trafficking and in control of protein translation. Changes were not seen in mice expressing the pathogenic G2019S LRRK2 mutation. Using cultured epithelial kidney cells, we replicated the accumulation of lysosomal proteases and demonstrated changes in subcellular distribution of the cation-independent mannose-6-phosphate receptor. These results show that loss of LRRK2 leads to co-ordinated responses in protein translation and trafficking and argue against a dominant negative role for the G2019S mutation.
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Registered trials
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.