ArticleNature communications2022
Small soluble α-synuclein aggregates are the toxic species in Parkinson's disease.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis that pooled it.
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Who cites it
137 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A bibliometric analysis of alpha-synuclein in Parkinson's disease from 2015 to 2024.Frontiers in neurologyPooled it
- Phase 1, randomized trials of MEDI1341: cerebrospinal fluid free α-synuclein lowered by >50.Brain communications · 2025Trial
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Probing the Energy Landscape of α-Synuclein Amyloid Fibril Formation by Systematic K-to-Q Mutagenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- Chlorogenic Acid Fails to Confer Neuroprotection in a Chronic Mouse Model of Parkinson's Disease.Molecular neurobiology · 2026Article
- Targeting soluble misfolded oligomers in anti-amyloid research.Nature reviews. Chemistry · 2026Review
- Large-scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of αSynuclein aggregation.FEBS open bio · 2026Article
- Pathogenic landscape shaped by cerebral amyloid oligomers.Neural regeneration research · 2026Article
- Tracking Gene Expression of Single Mitochondria in Live Neurons Using Nanotweezers.Journal of the American Chemical Society · 2026Article
- Single-molecule detection methods to study alpha-synuclein aggregation in postmortem Parkinson's disease brains.Cell reports methods · 2026Article
- Soluble α-synuclein oligomers drive transient corticostriatal pathology and delayed nigral vulnerability in a mouse model of early α-synucleinopathy.Acta neuropathologica communications · 2026Article
- Mechanism-selective inhibition of α-synuclein aggregation by the chaperone-like BRICHOS domain.The Journal of biological chemistry · 2026Article
- A Rigid Supramolecular Solution to a Flexible Problem: A Multifunctional Calix[4]arene-Based Strategy to Prevent α‑Synuclein Toxicity.ACS central science · 2026Article
- Redesign of TALE proteins for DNA-templated assembly of protein fibers.Nature communications · 2026Article
- Nanoscale CabioRxiv : the preprint server for biology · 2026Article
- Cell-based regenerative interventions in Parkinson's disease: Overcoming pharmacological limitations.Acta pharmaceutica Sinica. B · 2026Review
- Distinct Molecular Mechanisms Underlie Modulation of Seeded α-Synuclein Aggregation and Toxicity by Salvianolic Acid B and Dihydromyricetin.International journal of molecular sciences · 2026Article
- von Willebrand Factor fibers formed at pathological high shear provide a scaffold for α-synuclein binding and aggregation.Scientific reports · 2026Article
77 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Soluble α-synuclein aggregates varying in size, structure, and morphology have been closely linked to neuronal death in Parkinson's disease. However, the heterogeneity of different co-existing aggregate species makes it hard to isolate and study their individual toxic properties. Here, we show a reliable non-perturbative method to separate a heterogeneous mixture of protein aggregates by size. We find that aggregates of wild-type α-synuclein smaller than 200 nm in length, formed during an in vitro aggregation reaction, cause inflammation and permeabilization of single-liposome membranes and that larger aggregates are less toxic. Studying soluble aggregates extracted from post-mortem human brains also reveals that these aggregates are similar in size and structure to the smaller aggregates formed in aggregation reactions in the test tube. Furthermore, we find that the soluble aggregates present in Parkinson's disease brains are smaller, largely less than 100 nm, and more inflammatory compared to the larger aggregates present in control brains. This study suggests that the small non-fibrillar α-synuclein aggregates are the critical species driving neuroinflammation and disease progression.
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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.