ArticleJournal of neurochemistry2012
α-Synuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: relevance to human synucleopathic diseases.
Article in Journal of neurochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 114 citations in OpenAlex.
- α-Synuclein oligomers slow down action potential firing and enhance dopamine release by increasing Cav2.2 currents in midbrain dopaminergic neurons.The Journal of physiology · 2026Article
- Perivascular spread of CSF-derived α-synuclein oligomers drives region-specific Parkinson's-like pathology.NPJ Parkinson's disease · 2026Article
- In situ exogenous alpha-synuclein aggregates inhibit murine ventricular voltage-gated inward sodium and outward potassium currents.Journal of Parkinson's disease · 2025Article
- Tauopathies: Calmodulin Regulates Tau Hyperphosphorylation and Its Transformation into Disease-Specific Aggregates.Biomolecules · 2025Review
- Trace amine-associated receptor 1 (TAAR1): an emerging therapeutic target for neurodegenerative, neurodevelopmental, and neurotraumatic disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Calcineurin-mediated regulation of growth-associated protein 43 is essential for neurite and synapse formation and protects against α-synuclein-induced degeneration.Frontiers in aging neuroscience · 2025Article
- Inhibition of Calcineurin with FK506 Reduces Tau Levels and Attenuates Synaptic Impairment Driven by Tau Oligomers in the Hippocampus of Male Mouse Models.International journal of molecular sciences · 2024Article
- Article
- Exploration of Resveratrol as a Potent Modulator of α-Synuclein Fibril Formation.ACS chemical neuroscience · 2024Article
- Reduced Prevalence of Parkinson's Disease in Patients Prescribed Calcineurin Inhibitors.Journal of Parkinson's disease · 2024Article
- Intranasal administration of trehalose reduces α-synuclein oligomers and accelerates α-synuclein aggregation.Brain communications · 2024Article
- The alpha-synuclein oligomers activate nuclear factor of activated T-cell (NFAT) modulating synaptic homeostasis and apoptosis.Molecular medicine (Cambridge, Mass.) · 2023Article
- Simultaneous Determination of the Size and Shape of Single α-Synuclein Oligomers in Solution.ACS nano · 2023Article
- Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Alpha Synuclein: Neurodegeneration and Inflammation.International journal of molecular sciences · 2023Review
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration.International journal of molecular sciences · 2023Article
- Translating Pathological Brain Activity Primers in Parkinson's Disease Research.Research (Washington, D.C.) · 2023Review
- Harnessing IGF-1 and IL-2 as biomarkers for calcineurin activity to tailor optimal FK506 dosage in α-synucleinopathies.Frontiers in molecular biosciences · 2023Article
- Development of a novel pharmacophore model to screen specific inhibitors for the serine-threonine protein phosphatase calcineurin.Biochemistry and biophysics reports · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Intracellular deposition of fibrillar aggregates of α-synuclein (αSyn) characterizes neurodegenerative diseases such as Parkinson's disease (PD) and dementia with Lewy bodies. However, recent evidence indicates that small αSyn oligomeric aggregates that precede fibril formation may be the most neurotoxic species and can be found extracellularly. This new evidence has changed the view of pathological αSyn aggregation from a self-contained cellular phenomenon to an extracellular event and prompted investigation of the putative effects of extracellular αSyn oligomers. In this study, we report that extracellular application of αSyn oligomers detrimentally impacts neuronal welfare and memory function. We found that oligomeric αSyn increased intracellular Ca(2+) levels, induced calcineurin (CaN) activity, decreased cAMP response element-binding protein (CREB) transcriptional activity and resulted in calcineurin-dependent death of human neuroblastoma cells. Similarly, CaN induction and CREB inhibition were observed when αSyn oligomers were applied to organotypic brain slices, which opposed hippocampal long-term potentiation. Furthermore, αSyn oligomers induced CaN, inhibited CREB and evoked memory impairments in mice that received acute intracerebroventricular injections. Notably, all these events were reversed by pharmacological inhibition of CaN. Moreover, we found decreased active CaN and reduced levels of phosphorylated CREB in autopsy brain tissue from patients affected by dementia with Lewy bodies, which is characterized by deposition of αSyn aggregates and progressive cognitive decline. These results indicate that exogenously applied αSyn oligomers impact neuronal function and produce memory deficits through mechanisms that involve CaN activation.
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