ArticleJournal of cell science2015
Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition.
Article in Journal of cell science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
126 citing papers in PubMed, 2 syntheses or guidelines pooled it, 174 citations in OpenAlex.
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
- Allosteric switching of CaThe EMBO journal · 2026Article
- Organelle contact sites in cancer cells.Cell death & disease · 2026Review
- Article
- Functional single nucleotide polymorphisms in CACNA2D3 and other autophagy-related genes are associated with leprosy among Brazilians.PLoS neglected tropical diseases · 2026Article
- Investigating the ageing-Parkinson's disease nexus: standardisation of in vitro models and techniques by the PD-AGE network.NPJ Parkinson's disease · 2025Review
- The Two-Pore Channel 2 in Human Physiology and Diseases: Functional Characterisation and Pharmacology.International journal of molecular sciences · 2025Review
- MAPL regulates gasdermin-mediated release of mtDNA from lysosomes to drive pyroptotic cell death.Nature cell biology · 2025Article
- Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson's disease.The Journal of cell biology · 2025Article
- Disease-specific neuropathological alterations of the locus coeruleus in Alzheimer's disease, Down syndrome, and Parkinson's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Transcriptome signatures of human neural stem cells derived from LRRK2 gene therapeutic cells.Scientific reports · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- From Molecular Therapies to Lysosomal Transplantation and Targeted Drug Strategies: Present Applications, Limitations, and Future Prospects of Lysosomal Medications.Biomolecules · 2025Review
- Lysosome-associated CASM: from upstream triggers to downstream effector mechanisms.Frontiers in cell and developmental biology · 2025Review
- Lysosomal Channels as New Molecular Targets in the Pharmacological Therapy of Neurodegenerative DiseasesCurrent neuropharmacology · 2025Review
- CalDAG-GEFI acts as a guanine nucleotide exchange factor for LRRK2 to regulate LRRK2 function and neurodegeneration.Science advances · 2024Article
- Mechanisms of lysosomal tubulation and sorting driven by LRRK2.Biochemical Society transactions · 2024Review
- Plasticity of the selectivity filter is essential for permeation in lysosomal TPC2 channels.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Two-pore channels (TPCs) are endolysosomal ion channels implicated in Ca(2+) signalling from acidic organelles. The relevance of these ubiquitous proteins for human disease, however, is unclear. Here, we report that lysosomes are enlarged and aggregated in fibroblasts from Parkinson disease patients with the common G2019S mutation in LRRK2. Defects were corrected by molecular silencing of TPC2, pharmacological inhibition of TPC regulators [Rab7, NAADP and PtdIns(3,5)P2] and buffering local Ca(2+) increases. NAADP-evoked Ca(2+) signals were exaggerated in diseased cells. TPC2 is thus a potential drug target within a pathogenic LRRK2 cascade that disrupts Ca(2+)-dependent trafficking in Parkinson disease.
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What OpenQuestion holds
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.