ReviewTranslational neurodegeneration2022
LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson's disease.
Review in Translational neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Classification and Genotype-Phenotype Relationships of GBA1 Variants: MDSGene Systematic Review.Movement disorders : official journal of the Movement Disorder Society · 2025Pooled it
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- Interplay of GBA1 with lysosomal dysfunction and inflammation in Parkinson's disease.Neural regeneration research · 2026Article
- Selective Neuronal Vulnerability to Alpha-Synuclein Pathology in Parkinson's Disease: A Critical Review of Mechanistic Rationale and Biomarker Stratification.Medical sciences (Basel, Switzerland) · 2026Review
- Diffusion Magnetic Resonance Imaging of Cortical Microstructure Differs in Nonmanifest and Manifest Genetic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Molecular Pathogenesis of Memory Impairment in Parkinson's Disease: An Exploration of Underlying Mechanisms.Health science reports · 2026Article
- Mechanistic of LRRK2-Mediated Pyroptosis Via the NLRP3/Caspase-1/GSDMD Pathway in Parkinson's Disease Progression.Inflammation · 2026Article
- Parkinson's-Linked LRRK2 and GBA1 Mutations Modulate the Peripheral Immune Response to Pseudomonas aeruginosa.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Role of Microglial Dysfunction in Parkinson's Disease: From Multifactorial Causes to Neurodegeneration.Neuroscience bulletin · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Organelle-Targeted Nanotherapeutics for Parkinson's Disease: From Pathogenesis to Preclinical Strategies and Translational Challenges.International journal of nanomedicine · 2026Review
- Decoding the brain's ATG8 paralog code: LC3-GABARAP specialization at synapses and the astrocyte-neuron interface.Frontiers in cell and developmental biology · 2026Review
- Underlying Mechanisms of GBA1 in Parkinson's Disease and Dementia with Lewy Bodies: Narrative Review.Genes · 2025Review
- Preconditioning with hydrogen gas produces cardioprotective effects through autophagy activation in rat cardiomyocytes.BMC pharmacology & toxicology · 2025Article
- Longitudinal decline in striatal DAT binding in LRRK2 Parkinson's disease: connections with CSF α-synuclein seeding activity.Journal of neurology · 2025Article
- Recent Advances in Autophagy and Immunotherapy for the Clearance of Aggregated α-Synuclein in Parkinson's Disease.Aging and disease · 2025Review
- Lysosomal glucocerebrosidase is needed for ciliary Hedgehog signaling: A convergent pathway contributing to Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- Unlocking Parkinson's disease: the role of microRNAs in regulation, diagnosis, and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Protective Effect of the LRRK2 Kinase Inhibition in Human Fibroblasts Bearing the Genetic Variant GBA1 K198E: Implications for Parkinson's Disease.Neuromolecular medicine · 2025Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson's disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab GTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in GBA reduce glucocerebrosidase (GCase) activity, leading to glucosylceramide accumulation, α-syn aggregation and broad autophagic abnormalities. LRRK2 and GBA influence each other: GCase activity is reduced in LRRK2 mutant cells, and LRRK2 kinase inhibition can alter GCase activity in GBA mutant cells. Clinically, LRRK2 G2019S mutation seems to modify the effects of GBA mutation, resulting in milder symptoms than those resulting from GBA mutation alone. However, dual mutation carriers have an increased risk of PD and earlier age of onset compared with single mutation carriers, suggesting an additive deleterious effect on the initiation of PD pathogenic processes. Crosstalk between LRRK2 and GBA in PD exists, but its exact mechanism is unclear. Drugs that inhibit LRRK2 kinase or activate GCase are showing efficacy in pre-clinical models. Since LRRK2 kinase and GCase activities are also altered in idiopathic PD (iPD), it remains to be seen if these drugs will be useful in disease modification of iPD.
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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.