ArticleInternational journal of molecular sciences2021
ATP13A2 Regulates Cellular α-Synuclein Multimerization, Membrane Association, and Externalization.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Polyamine metabolic enzyme SAT1 remodels the neuronal transcriptome and rescues α-synuclein toxicity in Drosophila.Amino acids · 2026Article
- Serum L-ornithine-derived polyamines as indicators of Parkinson disease progression.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Progress in modelling ATP13A2-linked neurodegeneration.NPJ Parkinson's disease · 2026Review
- Studies on intellectual disability identify variants in established genes as well as confirm candidature of new genes.Scientific reports · 2026Article
- Polyamine metabolic enzyme SAT1 remodels the neuronal transcriptome and rescues α-synuclein toxicity in Drosophila.Research square · 2026Article
- Two lysosomal genes ATP13A2 and GBA1 interact to drive neurodegeneration.Molecular neurodegeneration · 2026Article
- Polyamine Metabolism in Brain Health and Disease.Neuropharmacology and therapy · 2026Article
- Bridging the gap in Parkinson's disease research: from general pathophysiology to advanced 3d cell culture models.Cell communication and signaling : CCS · 2025Review
- Phenotype Differences Between ATP13A2 Heterozygous and Knockout Mice Across Aging.International journal of molecular sciences · 2025Article
- Ubiquitin-Proteasome-Mediated Protein Degradation and Disorders of the Central Nervous System.International journal of molecular sciences · 2025Review
- Epigenetic regulation of the respiratory chain by a mitochondrial distress-related redox signal.Frontiers in cell and developmental biology · 2025Article
- Molecular Behavior of α-Synuclein Is Associated with Membrane Transport, Lipid Metabolism, and Ubiquitin-Proteasome Pathways in Lewy Body Disease.International journal of molecular sciences · 2024Article
- Alpha-Synuclein Contribution to Neuronal and Glial Damage in Parkinson's Disease.International journal of molecular sciences · 2023Review
- The Molecular Role of Polyamines in Age-Related Diseases: An Update.International journal of molecular sciences · 2023Review
- Parkinson's disease-associated ATP13A2/PARK9 functions as a lysosomal HNature communications · 2023Article
- Genetic Evidence for Endolysosomal Dysfunction in Parkinson's Disease: A Critical Overview.International journal of molecular sciences · 2023Review
- Modulating Effects of Cancer-Derived Exosomal miRNAs and Exosomal Processing by Natural Products.Cancers · 2023Review
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
ATP13A2, a late endo-/lysosomal polyamine transporter, is implicated in a variety of neurodegenerative diseases, including Parkinson's disease and Kufor-Rakeb syndrome, an early-onset atypical form of parkinsonism. Loss-of-function mutations in ATP13A2 result in lysosomal deficiency as a consequence of impaired lysosomal export of the polyamines spermine/spermidine. Furthermore, accumulating evidence suggests the involvement of ATP13A2 in regulating the fate of α-synuclein, such as cytoplasmic accumulation and external release. However, no consensus has yet been reached on the mechanisms underlying these effects. Here, we aimed to gain more insight into how ATP13A2 is linked to α-synuclein biology in cell models with modified ATP13A2 activity. We found that loss of ATP13A2 impairs lysosomal membrane integrity and induces α-synuclein multimerization at the membrane, which is enhanced in conditions of oxidative stress or exposure to spermine. In contrast, overexpression of ATP13A2 wildtype (WT) had a protective effect on α-synuclein multimerization, which corresponded with reduced αsyn membrane association and stimulation of the ubiquitin-proteasome system. We also found that ATP13A2 promoted the secretion of α-synuclein through nanovesicles. Interestingly, the catalytically inactive ATP13A2 D508N mutant also affected polyubiquitination and externalization of α-synuclein multimers, suggesting a regulatory function independent of the ATPase and transport activity. In conclusion, our study demonstrates the impact of ATP13A2 on α-synuclein multimerization via polyamine transport dependent and independent functions.
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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 Socratic graph.