ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2018
14-3-3 Proteins Reduce Cell-to-Cell Transfer and Propagation of Pathogenic α-Synuclein.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 70 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Knockout of Rab27b exacerbates neuropathology in alpha-synuclein mouse models.Acta neuropathologica communications · 2026Article
- 14-3-3σ up-regulation in the temporal cortex associates with tau pathology and reactive astroglia in Lewy body disorders.Brain pathology (Zurich, Switzerland) · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- 14-3-3θ phosphorylation at S232 reduces its interactome and regulates axonal trafficking.Disease models & mechanisms · 2025Article
- 14-3-3 Proteins Negatively Regulate Microglial Activation via Inhibition of the NF-κB Pathway.Journal of neurochemistry · 2025Article
- A novel 14-3-3θ phosphomimetic mouse model demonstrates social dominance defects.Biology open · 2025Article
- A Theoretical and Practical Analysis of Membrane Protein Genes Altered in Neutrophils in Parkinson's Disease.Current issues in molecular biology · 2025Article
- Rab27b Promotes Lysosomal Function and Alpha-Synuclein Clearance in Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- 14-3-3θ phosphorylation exacerbates alpha-synuclein aggregation and toxicity.Neurobiology of disease · 2025Article
- Prion and "Prion-Like" Detection: From Conventional Methods to Microfluidics or Lab-on-Chip Platforms to Monitor Seeding and Spreading of Misfolded Proteins.Sub-cellular biochemistry · 2025Review
- 14-3-3τ as a Modulator of Early α-Synuclein Multimerization and Amyloid Formation.ACS chemical neuroscience · 2024Article
- Neuropathogenesis-on-chips for neurodegenerative diseases.Nature communications · 2024Review
- Prospective Role of PAK6 and 14-3-3γ as Biomarkers for Parkinson's Disease.Journal of Parkinson's disease · 2024Article
- Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments.Journal of the American Chemical Society · 2023Article
- Myo1d promotes alpha-synuclein transfer from brain microvascular endothelial cells to pericytes through tunneling nanotubes.iScience · 2023Article
- Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers.Nature communications · 2023Article
- HydRA: Deep-learning models for predicting RNA-binding capacity from protein interaction association context and protein sequence.Molecular cell · 2023Article
- How Organ-on-a-Chip Technology Can Assist in Studying the Role of the Glymphatic System in Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
α-Synuclein (αsyn) is the key protein that forms neuronal aggregates in the neurodegenerative disorders Parkinson's disease (PD) and dementia with Lewy bodies. Recent evidence points to the prion-like spread of αsyn from one brain region to another. Propagation of αsyn is likely dependent on release, uptake, and misfolding. Under normal circumstances, this highly expressed brain protein functions normally without promoting pathology, yet the underlying endogenous mechanisms that prevent αsyn spread are not understood. 14-3-3 proteins are highly expressed brain proteins that have chaperone function and regulate protein trafficking. In this study, we investigated the potential role of the 14-3-3 proteins in the regulation of αsyn spread using two models of αsyn spread. In a paracrine αsyn model, 14-3-3θ promoted release of αsyn complexed with 14-3-3θ. Despite higher amounts of released αsyn, extracellular αsyn showed reduced oligomerization and seeding capability, reduced internalization, and reduced toxicity in primary mixed-gender mouse neurons. 14-3-3 inhibition reduced the amount of αsyn released, yet released αsyn was more toxic and demonstrated increased oligomerization, seeding capability, and internalization. In the preformed fibril model, 14-3-3 θ reduced αsyn aggregation and neuronal death, whereas 14-3-3 inhibition enhanced αsyn aggregation and neuronal death in primary mouse neurons. 14-3-3s blocked αsyn spread to distal chamber neurons not exposed directly to fibrils in multichamber, microfluidic devices. These findings point to 14-3-3s as a direct regulator of αsyn propagation, and suggest that dysfunction of 14-3-3 function may promote αsyn pathology in PD and related synucleinopathies.
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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 OpenQuestion graph.