ArticleNPJ Parkinson's disease2022
LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson's disease.
Article in NPJ Parkinson's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Mitochondrial Quality Control Imbalance in the Heterogeneity of Parkinson's Disease: From Selective Vulnerability to Stratified Transformation.International journal of molecular sciences · 2026Review
- Plasma proteomics for Parkinson's disease classification: cross-cohort benchmarking of proteomic, transcriptomic, and multimodal models.NPJ Parkinson's disease · 2026Article
- Article
- LRRK2 kinase mediates increased GCase activity in microglia in response to IFNγ-induced proinflammatory stimulation.NPJ Parkinson's disease · 2026Article
- Integrated Biofluid Proteomics Identified Dynamic Functional Biomarkers ofmedRxiv : the preprint server for health sciences · 2025Article
- Long-term oral glucocerebrosidase activator reduces soluble α-synuclein oligomer accumulation in Parkinsonian LRRK2 mutant mouse brain.NPJ Parkinson's disease · 2025Article
- Interferon gamma stimulates coordinated changes in LRRK2, GCase, and cathepsin activities in idiopathic and genetic Parkinson's disease monocytes.NPJ Parkinson's disease · 2025Article
- Genome-Wide Association Study of Glucocerebrosidase Activity Modifiers.Molecular neurobiology · 2025Article
- LRRK2 kinase activity regulates Parkinson's disease-relevant lipids at the lysosome.Molecular neurodegeneration · 2025Article
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- The modifying effect of mutant LRRK2 on mutant GBA1-associated Parkinson disease.Human molecular genetics · 2025Article
- Developing nanobodies as allosteric molecular chaperones of glucocerebrosidase function.Nature communications · 2025Article
- Immune cell metabolic dysfunction in Parkinson's disease.Molecular neurodegeneration · 2025Review
- Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease.Translational neurodegeneration · 2024Review
- A potential patient stratification biomarker for Parkinson´s disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells.NPJ Parkinson's disease · 2024Article
- Rotenone Blocks the Glucocerebrosidase Enzyme and Induces the Accumulation of Lysosomes and Autophagolysosomes Independently of LRRK2 Kinase in HEK-293 Cells.International journal of molecular sciences · 2023Article
- LRRK2 and Parkinson's disease: from genetics to targeted therapy.Annals of clinical and translational neurology · 2023Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 5 countries.
Funding
Abstract
Leucine-rich repeat kinase 2 (LRRK2) is a kinase involved in different cellular functions, including autophagy, endolysosomal pathways, and immune function. Mutations in LRRK2 cause autosomal-dominant forms of Parkinson's disease (PD). Heterozygous mutations in GBA1, the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), are the most common genetic risk factors for PD. Moreover, GCase function is altered in idiopathic PD and in other genetic forms of the disease. Recent work suggests that LRRK2 kinase activity can regulate GCase function. However, both a positive and a negative correlation have been described. To gain insights into the impact of LRRK2 on GCase, we performed a comprehensive analysis of GCase levels and activity in complementary LRRK2 models, including (i) LRRK2 G2019S knock in (GSKI) mice, (ii) peripheral blood mononuclear cell (PBMCs), plasma, and fibroblasts from PD patients carrying LRRK2 G2019S mutation, (iii) patient iPSCs-derived neurons; (iv) endogenous and overexpressed cell models. In some of these models we found a positive correlation between the activities of LRRK2 and GCase, which was further confirmed in cell lines with genetic and pharmacological manipulation of LRRK2 kinase activity. GCase protein level is reduced in GSKI brain tissues and in G2019S iPSCs-derived neurons, but increased in fibroblasts and PBMCs from patients, suggesting cell-type-specific effects. Overall, our study indicates that LRRK2 kinase activity affects both the levels and the catalytic activity of GCase in a cell-type-specific manner, with important implications in the context of therapeutic application of LRRK2 inhibitors in GBA1-linked and idiopathic PD.
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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.