ArticleBrain : a journal of neurology2018
Reduced LRRK2 in association with retromer dysfunction in post-mortem brain tissue from LRRK2 mutation carriers.
Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Possible linking and treatment between Parkinson's disease and inflammatory bowel disease: a study of Mendelian randomization based on gut-brain axis.Journal of translational medicine · 2025Pooled it
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- LRRK2 kinase-mediated accumulation of lysosome-associated phospho-Rabs in tauopathies and synucleinopathies.Acta neuropathologica · 2025Article
- Article
- Role of LRRK2 in axonal transport and Parkinson's disease.The Biochemical journal · 2025Review
- Leucine-rich repeat kinase 2 biomarkers for Parkinson's disease.The Biochemical journal · 2025Review
- Role of the Insulin-like Growth Factor System in Neurodegenerative Disease.International journal of molecular sciences · 2024Review
- Lysosomal storage, impaired autophagy and innate immunity in Gaucher and Parkinson's diseases: insights for drug discovery.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Retromer-dependent lysosomal stress in Parkinson's disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- OXR1 maintains the retromer to delay brain aging under dietary restriction.Nature communications · 2024Article
- ATP13A2 (PARK9) and basal ganglia function.Frontiers in neurology · 2023Review
- LRRK2 and Lipid Pathways: Implications for Parkinson's Disease.Biomolecules · 2022Review
- Retromer dysfunction in amyotrophic lateral sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Seventy-Two-Hour LRRK2 Kinase Activity Inhibition Increases Lysosomal GBA Expression in H4, a Human Neuroglioma Cell Line.International journal of molecular sciences · 2022Article
- Increased expression of pathological markers in Parkinson's disease dementia post-mortem brains compared to dementia with Lewy bodies.BMC neuroscience · 2022Article
- Beware of Misdelivery: Multifaceted Role of Retromer Transport in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2022Review
- Retromer dependent changes in cellular homeostasis and Parkinson's disease.Essays in biochemistry · 2021Review
- LRRK2 along the Golgi and lysosome connection: a jamming situation.Biochemical Society transactions · 2021Review
- Endosomal traffic and glutamate synapse activity are increased in VPS35 D620N mutant knock-in mouse neurons, and resistant to LRRK2 kinase inhibition.Molecular brain · 2021Article
- Oligomerization of Lrrk controls actin severing and α-synuclein neurotoxicity in vivo.Molecular neurodegeneration · 2021Article
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Authors and funding
12 authors at 8 institutions in 4 countries.
Funding
Abstract
Missense mutations in leucine-rich repeat kinase 2 (LRRK2) are pathogenic for familial Parkinson's disease. However, it is unknown whether levels of LRRK2 protein in the brain are altered in patients with LRRK2-associated Parkinson's disease. Because LRRK2 mutations are relatively rare, accounting for approximately 1% of all Parkinson's disease, we accessioned cases from five international brain banks to investigate levels of the LRRK2 protein, and other genetically associated Parkinson's disease proteins. Brain tissue was obtained from 17 LRRK2 mutation carriers (12 with the G2019S mutation and five with the I2020T mutation) and assayed by immunoblot. Compared to matched controls and idiopathic Parkinson's disease cases, we found levels of LRRK2 protein were reduced in the LRRK2 mutation cases. We also measured a decrease in two other proteins genetically implicated in Parkinson's disease, the core retromer component, vacuolar protein sorting associated protein 35 (VPS35), and the lysosomal hydrolase, glucocerebrosidase (GBA). Moreover, the classical retromer cargo protein, cation-independent mannose-6-phosphate receptor (MPR300, encoded by IGF2R), was also reduced in the LRRK2 mutation cohort and protein levels of the receptor were correlated to levels of LRRK2. These results provide new data on LRRK2 protein expression in brain tissue from LRRK2 mutation carriers and support a relationship between LRRK2 and retromer dysfunction in LRRK2-associated Parkinson's disease brain.
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