ArticleHuman molecular genetics2016
Synphilin-1 attenuates mutant LRRK2-induced neurodegeneration in Parkinson's disease models.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Integrated omics-driven discovery reveals synphilin-1-mediated anoikis resistance through p53 down-regulation.Bioscience reports · 2026Article
- Synphilin-1 mitigates autophagy dysfusnction, modulates ubiquitinated protein aggregation, and promotes cell survival during proteotoxic stress.bioRxiv : the preprint server for biology · 2026Article
- Synphilin-1 Is Essential for Cytoskeletal Integrity of Brain Ventricular Cilia and Mitochondrial Proteostasis.International journal of molecular sciences · 2026Article
- Synphilin-1 modulates alpha-synuclein assembly, release and uptake.NPJ Parkinson's disease · 2025Article
- MicroRNA-Targeted Gene Regulation in Salivary Gland Tissue of De Novo Parkinson's Disease Patients.Molecular neurobiology · 2025Article
- Maturation and detoxification of synphilin-1 inclusion bodies regulated by sphingolipids.eLife · 2025Article
- A-Syn(ful) MAM: A Fresh Perspective on a Converging Domain in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson's Disease.Biomolecules · 2024Review
- Whole Exome Sequencing Study Identifies Novel Rare Risk Variants for Habitual Coffee Consumption Involved in Olfactory Receptor and Hyperphagia.Nutrients · 2022Article
- Yeasts as Complementary Model Systems for the Study of the Pathological Repercussions of Enhanced Synphilin-1 Glycation and Oxidation.International journal of molecular sciences · 2021Article
- Article
- Analysis of master transcription factors related to Parkinson's disease through the gene transcription regulatory network.Archives of medical science : AMS · 2021Article
- Curcumin Reduced HFrontiers in aging neuroscience · 2021Article
- Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation.International journal of molecular sciences · 2020Article
- MicroRNA-150 serves as a diagnostic biomarker and is involved in the inflammatory pathogenesis of Parkinson's disease.Molecular genetics & genomic medicine · 2020Article
- Transmembrane Protein 230 Mediates a Poly(ADP-ribose) Polymerase-1-Linked Apoptosis.Frontiers in aging neuroscience · 2020Article
- Article
- IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson's disease.Cell death & disease · 2019Article
- Bioinformatic gene analysis for potential biomarkers and therapeutic targets of atrial fibrillation-related stroke.Journal of translational medicine · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant Parkinsonism with pleomorphic pathology including deposits of aggregated protein and neuronal degeneration. The pathogenesis of LRRK2-linked Parkinson's disease (PD) is not fully understood. Here, using co-immunoprecipitation, we found that LRRK2 interacted with synphilin-1 (SP1), a cytoplasmic protein that interacts with α-synuclein and has implications in PD pathogenesis. LRRK2 interacted with the N-terminus of SP1 whereas SP1 predominantly interacted with the C-terminus of LRRK2, including kinase domain. Co-expression of SP1 with LRRK2 increased LRRK2-induced cytoplasmic aggregation in cultured cells. Moreover, SP1 also attenuated mutant LRRK2-induced toxicity and reduced LRRK2 kinase activity in cultured cells. Knockdown of SP1 by siRNA enhanced LRRK2 neuronal toxicity. In vivo Drosophila studies, co-expression of SP1 and mutant G2019S-LRRK2 in double transgenic Drosophila increased survival and improved locomotor activity. Expression of SP1 protects against G2019S-LRRK2-induced dopamine neuron loss and reduced LRRK2 phosphorylation in double transgenic fly brains. Our findings demonstrate that SP1 attenuates mutant LRRK2-induced PD-like phenotypes and plays a neural protective role.
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Registered trials
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