ArticleThe Journal of biological chemistry2014
Anti-amyloid compounds inhibit α-synuclein aggregation induced by protein misfolding cyclic amplification (PMCA).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies.Frontiers in aging neuroscience · 2022Pooled it
- Identification of small molecule dimethyoxyphenyl piperazine inhibitors of alpha-synuclein fibril growth.Scientific reports · 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
- Seed Amplification Assays as Powerful Tools for Detecting Peripheral Biomarkers in Prion-Like Diseases.Sub-cellular biochemistry · 2025Review
- Targeting Protein Misfolding and Aggregation as a Therapeutic Perspective in Neurodegenerative Disorders.International journal of molecular sciences · 2024Review
- The potential of phosphorylated α-synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy.CNS neuroscience & therapeutics · 2024Review
- Exploration of Resveratrol as a Potent Modulator of α-Synuclein Fibril Formation.ACS chemical neuroscience · 2024Article
- Biomarkers for parkinsonian disorders in CNS-originating EVs: promise and challenges.Acta neuropathologica · 2023Review
- Quaternary structure of patient-homogenate amplified α-synuclein fibrils modulates seeding of endogenous α-synuclein.Communications biology · 2022Article
- RT-QuIC and Related Assays for Detecting and Quantifying Prion-like Pathological Seeds of α-Synuclein.Biomolecules · 2022Review
- Potent inhibitors of toxic alpha-synuclein identified via cellular time-resolved FRET biosensors.NPJ Parkinson's disease · 2021Article
- An intact membrane is essential for small extracellular vesicle-induced modulation of α-synuclein fibrillization.Journal of extracellular vesicles · 2020Article
- Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling.Nature communications · 2020Article
- Analysis of Protein Conformational Strains-A Key for New Diagnostic Methods of Human Diseases.International journal of molecular sciences · 2020Article
- Imaging Flow Cytometry Illuminates New Dimensions of Amyloid Peptide-Membrane Interactions.Biophysical journal · 2020Article
- Misfolded α-synuclein causes hyperactive respiration without functional deficit in live neuroblastoma cells.Disease models & mechanisms · 2020Article
- α-Synuclein strains target distinct brain regions and cell types.Nature neuroscience · 2020Article
- Inhibition of α-Synuclein Aggregation and Mature Fibril Disassembling With a Minimalistic Compound, ZPDm.Frontiers in bioengineering and biotechnology · 2020Article
- Gut Microbiome-Modified Polyphenolic Compounds Inhibit α-Synuclein Seeding and Spreading in α-Synucleinopathies.Frontiers in neuroscience · 2020Article
- Structural heterogeneity of α-synuclein fibrils amplified from patient brain extracts.Nature communications · 2019Article
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Authors and funding
6 authors.
Funding
Abstract
Filaments made of α-synuclein form the characteristic Lewy pathology in Parkinson and other diseases. The formation of α-synuclein filaments can be reproduced in vitro by incubation of recombinant protein, but the filament growth is very slow and highly variable and so unsuitable for fast high throughput anti-aggregation drug screening. To overcome this obstacle we have investigated whether the protein misfolding cyclic amplification (PMCA) technique, used for fast amplification of prion protein aggregates, could be adapted for growing α-synuclein aggregates and thus suitable for screening of drugs to affect α-synuclein aggregation for the treatment of the yet incurable α-synucleinopathies. Circular dichroism, electron microscopy, and native and SDS-polyacrylamide gels were used to demonstrate α-synuclein aggregate formation by PMCA, and the strain imprint of the α-synuclein fibrils was studied by proteinase K digestion. We also demonstrated that α-synuclein fibrils are able to seed new α-synuclein PMCA reactions and to enter and aggregate in cells in culture. In particular, we have generated a line of "chronically infected" cells, which transmit α-synuclein aggregates even after multiple passages. To evaluate the sensitivity of the PMCA system as an α-synuclein anti-aggregating drug screening assay a panel of 10 drugs was tested. Anti-amyloid compounds proved efficient in inhibiting α-synuclein fibril formation induced by PMCA. Our results show that α-synuclein PMCA is a fast and reproducible system that could be used as a high throughput screening method for finding new α-synuclein anti-aggregating compounds.
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