ArticleBiochimica et biophysica acta2013
Inhibition of LRRK2 kinase activity stimulates macroautophagy.
Article in Biochimica et biophysica acta, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 147 citations in OpenAlex.
- LRRK2: Molecular Mechanisms in Parkinson's Disease.International journal of molecular sciences · 2026Review
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- Autophagy Dysfunction and Neurodegeneration: Where Does It Go Wrong?Journal of molecular biology · 2025Review
- Cadmium exposure following early-life respiratory syncytial virus infection promotes lung fibrosis through autophagy inhibition.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Role of LRRK2 in axonal transport and Parkinson's disease.The Biochemical journal · 2025Review
- The role of autophagy in brain health and disease: Insights into exosome and autophagy interactions.Heliyon · 2024Review
- Lysosomal dysfunction in α-synuclein pathology: molecular mechanisms and therapeutic strategies.Cellular and molecular life sciences : CMLS · 2024Review
- Biphenotypic Cells and α-Synuclein Accumulation in Enteric Neurons of Leucine-Rich Repeat Kinase 2 Knockout Mice.Digestive diseases and sciences · 2024Article
- TIGAR exacerbates obesity by triggering LRRK2-mediated defects in macroautophagy and chaperone-mediated autophagy in adipocytes.Autophagy · 2024Article
- The Potential of Targeting Autophagy-Related Non-coding RNAs in the Treatment of Alzheimer's and Parkinson's Diseases.Cellular and molecular neurobiology · 2024Review
- Article
- Role of Astrogliosis in the Pathogenesis of Parkinson's Disease: Insights into Astrocytic Nrf2 Pathway as a Potential Therapeutic Target.CNS & neurological disorders drug targets · 2024Review
- Parkinson's disease therapy: what lies ahead?Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- Role of Astrocytes in Parkinson's Disease Associated with Genetic Mutations and Neurotoxicants.Cells · 2023Review
- Tissue specific LRRK2 interactomes reveal a distinct striatal functional unit.PLoS computational biology · 2023Article
- Brain Energy Metabolism: Astrocytes in Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2023Review
- The parkinsonian LRRK2 R1441G mutation shows macroautophagy-mitophagy dysregulation concomitant with endoplasmic reticulum stress.Cell biology and toxicology · 2022Article
- The emerging role of LRRK2 in tauopathies.Clinical science (London, England : 1979) · 2022Review
- Seventy-Two-Hour LRRK2 Kinase Activity Inhibition Increases Lysosomal GBA Expression in H4, a Human Neuroglioma Cell Line.International journal of molecular sciences · 2022Article
- LRRK2 and Proteostasis in Parkinson's Disease.International journal of molecular sciences · 2022Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Leucine Rich Repeat Kinase 2 (LRRK2) is one of the most important genetic contributors to Parkinson's disease. LRRK2 has been implicated in a number of cellular processes, including macroautophagy. To test whether LRRK2 has a role in regulating autophagy, a specific inhibitor of the kinase activity of LRRK2 was applied to human neuroglioma cells and downstream readouts of autophagy examined. The resulting data demonstrate that inhibition of LRRK2 kinase activity stimulates macroautophagy in the absence of any alteration in the translational targets of mTORC1, suggesting that LRRK2 regulates autophagic vesicle formation independent of canonical mTORC1 signaling. This study represents the first pharmacological dissection of the role LRRK2 plays in the autophagy/lysosomal pathway, emphasizing the importance of this pathway as a marker for LRRK2 physiological function. Moreover it highlights the need to dissect autophagy and lysosomal activities in the context of LRRK2 related pathologies with the final aim of understanding their aetiology and identifying specific targets for disease modifying therapies in patients.
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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.