ArticleNeuroscience2012
Lewy-like aggregation of α-synuclein reduces protein phosphatase 2A activity in vitro and in vivo.
Article in Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Network Analysis Identifies Disease-Specific Pathways for Parkinson's Disease.Molecular neurobiology · 2018Pooled it
- TogoPhosTAC as a delivery-ready platform for targeted protein dephosphorylation.Nature communications · 2026Article
- Protein phosphatase 2A methylation state impacts α-synucleinopathy in mouse models.Cell death discovery · 2026Article
- Magnetoreceptive CRY/MagR complexes: linking circadian redox signalling to protein aggregation in Alzheimer's and Parkinson's disease.ADMET & DMPK · 2026Review
- Converging pathologies in neurodegeneration: the mechanistic interplay between α-Synuclein and Tau in Alzheimer's and Parkinson's.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Neuroprotective efficacy of berberine and caffeine against rotenone-induced neuroinflammatory and oxidative disturbances associated with Parkinson's disease via inhibiting α-synuclein aggregation and boosting dopamine release.Inflammopharmacology · 2025Article
- New insights on the potential anti-epileptic effect of metformin: Mechanistic pathway.Journal of cellular and molecular medicine · 2023Review
- PTEN-Induced Putative Kinase 1 Dysfunction Accelerates Synucleinopathy.Journal of Parkinson's disease · 2022Article
- Prolyl oligopeptidase inhibition reduces alpha-synuclein aggregation in a cellular model of multiple system atrophy.Journal of cellular and molecular medicine · 2021Article
- All Roads Lead to Rome: Different Molecular Players Converge to Common Toxic Pathways in Neurodegeneration.Cells · 2021Review
- PP2A and Its Inhibitors in Helper T-Cell Differentiation and Autoimmunity.Frontiers in immunology · 2021Review
- Molecular crosstalk between cancer and neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2020Review
- FTY720-Mitoxy reduces synucleinopathy and neuroinflammation, restores behavior and mitochondria function, and increases GDNF expression in Multiple System Atrophy mouse models.Experimental neurology · 2020Article
- Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration.Pharmacology & therapeutics · 2019Review
- The role of posttranslational modifications of α-synuclein and LRRK2 in Parkinson's disease: Potential contributions of environmental factors.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- FTY720 Improves Behavior, Increases Brain Derived Neurotrophic Factor Levels and Reduces α-Synuclein Pathology in Parkinsonian GM2+/- Mice.Neuroscience · 2019Article
- To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling.Cellular and molecular life sciences : CMLS · 2019Review
- Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson's disease and schizophrenia.Neuropsychiatric disease and treatment · 2019Article
- Parkinsonian GM2 synthase knockout mice lacking mature gangliosides develop urinary dysfunction and neurogenic bladder.Experimental neurology · 2019Article
- Targeting PP2A in cancer: Combination therapies.Biochimica et biophysica acta. Molecular cell research · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
α-synuclein (α-Syn) is a chaperone-like protein that is highly implicated in Parkinson's disease (PD) as well as in dementia with Lewy bodies (DLB). Rare forms of PD occur in individuals with mutations of α-Syn or triplication of wild type α-Syn, and in both PD and DLB the intraneuronal inclusions known as Lewy bodies contain aggregated α-Syn that is highly phosphorylated on serine 129. In neuronal cells and in the brains of α-Syn overexpressing transgenic mice, soluble α-Syn stimulates the activity of protein phosphatase 2A (PP2A), a major serine/threonine phosphatase. Serine 129 phosphorylation of α-Syn attenuates its stimulatory effects on PP2A and also accelerates α-Syn aggregation; however, it is unknown if aggregation of α-Syn into Lewy bodies impairs PP2A activity. To assess for this, we measured the impact of α-Syn aggregation on PP2A activity in vitro and in vivo. In cell-free assays, aggregated α-Syn had ∼50% less PP2A stimulatory effects than soluble recombinant α-Syn. Similarly in DLB and α-Syn triplication brains, which contain robust α-Syn aggregation with high levels of serine 129 phosphorylation, PP2A activity was also ∼50% attenuated. As α-Syn normally stimulates PP2A activity, our data suggest that overexpression of α-Syn or sequestration of α-Syn into Lewy bodies has the potential to alter the phosphorylation state of key PP2A substrates; raising the possibility that all forms of synucleinopathy will benefit from treatments aimed at optimizing PP2A 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.