ArticleCell stem cell2020
Defects in mRNA Translation in LRRK2-Mutant hiPSC-Derived Dopaminergic Neurons Lead to Dysregulated Calcium Homeostasis.
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Article in Cell stem cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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38citing papers in PubMed, 1 pooled it
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Spaceflight-relevant microgravity triggers a sublethal Parkinson's-like dopaminergic decline in human neurons and organoids.bioRxiv : the preprint server for biology · 2026Article
- The human LRRK2-R1441G mutation drives age-dependent oxidative stress and mitochondrial dysfunction in dopaminergic neurons.Molecular neurodegeneration · 2026Article
- Unraveling the core: hub genes bridging familial and sporadic Parkinson's disease.Journal of neurology · 2026Article
- Evolutionary hotspots of structural variation drive inter-individual differences in the expression of fusion transcripts in the human brain.Nucleic acids research · 2025Article
- Induced Pluripotent Stem Cells Derived Cellular Models for Investigating Parkinson's Disease Pathogenesis and Drug Screening.Stem cell reviews and reports · 2025Review
- Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson's disease.The Journal of cell biology · 2025Article
- Astrocytes carrying LRRK2 G2019S exhibit increased levels of clusterin chaperone via miR-22-5p and reduced ability to take up α-synuclein fibrils.Acta neuropathologica communications · 2025Article
- The Mitochondrial Foundations of Parkinson's Disease: Therapeutic Implications.Aging and disease · 2025Review
- The Multifaceted Role of LRRK2 in Parkinson's Disease.Brain sciences · 2025Review
- LRRK2 in Drosophila Melanogaster Model: Insights into Cellular Dysfunction and Neuroinflammation in Parkinson's Disease.International journal of molecular sciences · 2025Review
- CalDAG-GEFI acts as a guanine nucleotide exchange factor for LRRK2 to regulate LRRK2 function and neurodegeneration.Science advances · 2024Article
- Optical genome mapping of structural variants in Parkinson's disease-related induced pluripotent stem cells.BMC genomics · 2024Article
- The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders.Current issues in molecular biology · 2024Review
- A dysregulated calcium homeostasis as the earliest pathological sign in stem cell-derived Parkinson's disease neurons?Neural regeneration research · 2024Article
- Protein Translation in the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2024Review
- Interspecies chimerism with human embryonic stem cells generates functional human dopamine neurons at low efficiency.Stem cell reports · 2024Article
- Mitochondrial Calcium Transport During Autophagy Initiation.Mitochondrial communications · 2024Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Jungwoo Wren KimNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Xiling YinNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Aanishaa JhaldiyalNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Mohammed Repon KhanNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ian MartinNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Zhong XieDepartment of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Tamara Perez-RoselloDepartment of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Manoj KumarNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Leire Abalde-AtristainNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jinchong XuNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Li ChenNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Stephen M EackerNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA.
D James SurmeierDepartment of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Nicholas T IngoliaDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130, USA. Electronic address: tdawson@jhmi.edu.
Valina L DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130, USA. Electronic address: vdawson@jhmi.edu.
Johns Hopkins University · USNorthwestern University · USUniversity of California, Berkeley · US
Funding
Understanding Mechanisms of a-synuclein pathologyP50NS038377 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 1998 to 2019
$38.8MResearch Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Abhay Moghekar · 2020 to 2026
$29.3MRole of Elevated Diet-linked TOR Activity and Protein Synthesis in Parkinson's Disease NeurodegenerationK01AG050718 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI MARTIN, IAN · 2015 to 2019
$653kNIA NIH HHS K01 AG050718NIA NIH HHS P30 AG066507NINDS NIH HHS P50 NS038377
Abstract
The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is a common cause of familial Parkinson's disease (PD). This mutation results in dopaminergic neurodegeneration via dysregulated protein translation, although how alterations in protein synthesis contribute to neurodegeneration in human neurons is not known. Here we define the translational landscape in LRRK2-mutant dopaminergic neurons derived from human induced pluripotent stem cells (hiPSCs) via ribosome profiling. We found that mRNAs that have complex secondary structure in the 5' untranslated region (UTR) are translated more efficiently in G2019S LRRK2 neurons. This leads to the enhanced translation of multiple genes involved in Ca
Indexed as
Induced Pluripotent Stem CellsParkinson DiseaseCalciumDopaminergic NeuronsHomeostasisHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MutationProtein BiosynthesisCalciumLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, human5′ UTRcalcium homeostasisLRRK2Parkinson’s diseaseribosome profilingRPS15translatomeuS19
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