ArticleNeuron2019
Stress-Induced Cellular Clearance Is Mediated by the SNARE Protein ykt6 and Disrupted by α-Synuclein.
Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Meta-analysis and in-silico functional characterization of the SNCA variant rs356220 in Parkinson's disease.Scientific reports · 2025Pooled it
- Single-nucleus epigenomic dysregulation unmasks genetic risk-associated neurodegenerative glia states.Nature communications · 2026Article
- Statins and genetic inhibition of the mevalonate pathway activate an ATF3-STMN2 regenerative program.bioRxiv : the preprint server for biology · 2026Article
- YKT6 Is Essential for Male Fertility by Promoting Meiosis Progression During Spermatogenesis of Mice.Cell proliferation · 2026Article
- Research progress on the α-synuclein-lysosome axis in Parkinson's disease: molecular mechanisms of protein aggregation, autophagy dysfunction, and therapeutic targeting.Frontiers in neuroscience · 2026Review
- Failure of lysosomal acidification and endomembrane network in neurodegeneration.Experimental & molecular medicine · 2025Review
- C-terminus-dependent detection of lysosomal alpha-synuclein in nigral Parkinson's disease human brain neurons.Molecular neurodegeneration · 2025Article
- Novel Roles for Geranylgeranyl Transferase-III (GGTase-III) in Insulin Secretion.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2025Article
- Alpha-Synuclein Inhibits the Secretion of Extracellular Vesicles through Disruptions in YKT6 Lipidation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- α-Synuclein: Multiple pathogenic roles in trafficking and proteostasis pathways in Parkinson's disease.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Nuclear aggregates of NONO/SFPQ and A-to-I-edited RNA in Parkinson's disease and dementia with Lewy bodies.Neuron · 2024Article
- The hexosamine biosynthetic pathway rescues lysosomal dysfunction in Parkinson's disease patient iPSC derived midbrain neurons.Nature communications · 2024Article
- The Ykt6-Snap29-Syx13 SNARE complex promotes crinophagy via secretory granule fusion with Lamp1 carrier vesicles.Scientific reports · 2024Article
- Stress-related cellular pathophysiology as a crosstalk risk factor for neurocognitive and psychiatric disorders.BMC neuroscience · 2023Review
- Reciprocal effects of alpha-synuclein aggregation and lysosomal homeostasis in synucleinopathy models.Translational neurodegeneration · 2023Article
- Knocking out alpha-synuclein in melanoma cells downregulates L1CAM and decreases motility.Scientific reports · 2023Article
- Impaired Autophagic-Lysosomal Fusion in Parkinson's Patient Midbrain Neurons Occurs through Loss of ykt6 and Is Rescued by Farnesyltransferase Inhibition.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- RNAseq Analysis of FABP4 Knockout Mouse Hippocampal Transcriptome Suggests a Role for WNT/β-Catenin in Preventing Obesity-Induced Cognitive Impairment.International journal of molecular sciences · 2023Article
- Honokiol decreases alpha-synuclein mRNA levels and reveals novel targets for modulating alpha-synuclein expression.Frontiers in aging neuroscience · 2023Article
- Construction and validation of a risk model based on the key SNARE proteins to predict the prognosis and immune microenvironment of gliomas.Frontiers in molecular neuroscience · 2023Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Age-related neurodegenerative disorders are characterized by a slow, persistent accumulation of aggregated proteins. Although cells can elicit physiological responses to enhance cellular clearance and counteract accumulation, it is unclear how pathogenic proteins evade this process in disease. We find that Parkinson's disease α-synuclein perturbs the physiological response to lysosomal stress by impeding the SNARE protein ykt6. Cytosolic ykt6 is normally autoinhibited by a unique farnesyl-mediated regulatory mechanism; however, during lysosomal stress, it activates and redistributes into membranes to preferentially promote hydrolase trafficking and enhance cellular clearance. α-Synuclein aberrantly binds and deactivates ykt6 in patient-derived neurons, thereby disabling the lysosomal stress response and facilitating protein accumulation. Activating ykt6 by small-molecule farnesyltransferase inhibitors restores lysosomal activity and reduces α-synuclein in patient-derived neurons and mice. Our findings indicate that α-synuclein creates a permissive environment for aggregate persistence by inhibiting regulated cellular clearance and provide a therapeutic strategy to restore protein homeostasis by harnessing SNARE activity.
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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.