ReviewThe European journal of neuroscience2019
Induced pluripotent stem cell-based modeling of mutant LRRK2-associated Parkinson's disease.
Review in The European journal of neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- A genome-wide association study of young onset Parkinson's disease in European ancestry.medRxiv : the preprint server for health sciences · 2026Article
- Underlying Mechanisms of GBA1 in Parkinson's Disease and Dementia with Lewy Bodies: Narrative Review.Genes · 2025Review
- Low-frequency genetic variants in GAK enhance Golgi function and protect against Parkinson's disease.medRxiv : the preprint server for health sciences · 2025Article
- Morphological profiling reveals neuroprotection via mitochondrial uncoupling in human dopaminergic neurons.Scientific reports · 2025Article
- Monoamine Oxidase Inhibitors in Toxic Models of Parkinsonism.International journal of molecular sciences · 2025Review
- Seeing Neurodegeneration in a New Light Using Genetically Encoded Fluorescent Biosensors and iPSCs.International journal of molecular sciences · 2023Review
- High-content phenotyping of Parkinson's disease patient stem cell-derived midbrain dopaminergic neurons using machine learning classification.Stem cell reports · 2022Article
- Parkinson-causing mutations in LRRK2 impair the physiological tetramerization of endogenous α-synuclein in human neurons.NPJ Parkinson's disease · 2022Article
- Induced pluripotent stem cells for defining Parkinsonian patient subtypes: a further step toward precision medicine.Neural regeneration research · 2022Article
- Electrophysiological Properties of Induced Pluripotent Stem Cell-Derived Midbrain Dopaminergic Neurons Correlate With Expression of Tyrosine Hydroxylase.Frontiers in cellular neuroscience · 2022Article
- Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned?International journal of molecular sciences · 2021Review
- Development of a physiologically relevant and easily scalable LUHMES cell-based model of G2019S LRRK2-driven Parkinson's disease.Disease models & mechanisms · 2021Article
- A monolayer hiPSC culture system for autophagy/mitophagy studies in human dopaminergic neurons.Autophagy · 2021Article
- The Role of iPSC Modeling Toward Projection of Autophagy Pathway in Disease Pathogenesis: Leader or Follower.Stem cell reviews and reports · 2021Review
- Energy Metabolism Disturbances in Cell Models of PARK2 CNV Carriers with ADHD.Journal of clinical medicine · 2020Article
- Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson's Disease Patient-Derived iPSCs.Life (Basel, Switzerland) · 2020Article
- Patient-Derived Induced Pluripotent Stem Cell-Based Models in Parkinson's Disease for Drug Identification.International journal of molecular sciences · 2020Review
- Review
- Induced pluripotent stem cell-based modeling of mutant LRRK2-associated Parkinson's disease.The European journal of neuroscience · 2019Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Recent advances in cell reprogramming have enabled assessment of disease-related cellular traits in patient-derived somatic cells, thus providing a versatile platform for disease modeling and drug development. Given the limited access to vital human brain cells, this technology is especially relevant for neurodegenerative disorders such as Parkinson's disease (PD) as a tool to decipher underlying pathomechanisms. Importantly, recent progress in genome-editing technologies has provided an ability to analyze isogenic induced pluripotent stem cell (iPSC) pairs that differ only in a single genetic change, thus allowing a thorough assessment of the molecular and cellular phenotypes that result from monogenetic risk factors. In this review, we summarize the current state of iPSC-based modeling of PD with a focus on leucine-rich repeat kinase 2 (LRRK2), one of the most prominent monogenetic risk factors for PD linked to both familial and idiopathic forms. The LRRK2 protein is a primarily cytosolic multi-domain protein contributing to regulation of several pathways including autophagy, mitochondrial function, vesicle transport, nuclear architecture and cell morphology. We summarize iPSC-based studies that contributed to improving our understanding of the function of LRRK2 and its variants in the context of PD etiopathology. These data, along with results obtained in our own studies, underscore the multifaceted role of LRRK2 in regulating cellular homeostasis on several levels, including proteostasis, mitochondrial dynamics and regulation of the cytoskeleton. Finally, we expound advantages and limitations of reprogramming technologies for disease modeling and drug development and provide an outlook on future challenges and expectations offered by this exciting technology.
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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.