ArticleNature communications2022
The clinical drug candidate anle138b binds in a cavity of lipidic α-synuclein fibrils.
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 36 papers.
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Who cites it
36 citing papers in PubMed, 51 citations in OpenAlex.
- A Live-Cell Imaging System for the Identification of Pro- and Anti-Aggregatory α-Synuclein Modulators.Molecular neurobiology · 2026Article
- From synaptic development to degeneration: a narrative review of small molecule strategies targeting alpha-synuclein in Parkinson's disease.Metabolic brain disease · 2026Review
- Targeted molecular docking-guided insights into the antioxidant reparative mechanisms ofBiochemistry and biophysics reports · 2026Article
- PET imaging of alpha-synuclein: from radiotracer design through in vitro and in vivo translation.European journal of nuclear medicine and molecular imaging · 2026Review
- Foldamers rescue synucleinopathy phenotypes in multiple in vitro and in vivo models.Science translational medicine · 2026Article
- pH Sensitivity of the SERF1a Conformational Ensemble.ACS omega · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Therapeutic strategies in prion disease: current evidence, translational challenges, and emerging directions.Frontiers in neuroscience · 2026Review
- Anle138b mitigates post-hypoxic cognitive impairment, α-Synuclein aggregation and UPR activation in Drosophila melanogaster.Acta neuropathologica communications · 2025Article
- "Coordination of Anle138b to Silver Results in Selective Reduction of a C-terminal truncated Alpha-synuclein Protein and Increased Aggregate Size."bioRxiv : the preprint server for biology · 2025Article
- Anle138b binds predominantly to the central cavity in lipidic Aβ₄₀ fibrils and modulates fibril formation.Nature communications · 2025Article
- Neuroprotection in Parkinson Disease.Neurology and therapy · 2025Review
- Alpha-synuclein fibril structures cluster into distinct classes.Biophysical journal · 2025Review
- Recent Advances in Autophagy and Immunotherapy for the Clearance of Aggregated α-Synuclein in Parkinson's Disease.Aging and disease · 2025Review
- A mechanistic model of pure and lipidic α-synuclein aggregation for advancing Parkinson's therapies.Communications chemistry · 2025Article
- Ligands for Protein Fibrils of Amyloid-β, α-Synuclein, and Tau.Chemical reviews · 2025Review
- Exploring the Potential of Biomimetic Peptides in Targeting Fibrillar and Filamentous Alpha-Synuclein-An In Silico and Experimental Approach to Parkinson's Disease.Biomimetics (Basel, Switzerland) · 2024Article
- Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, tau and alpha-synuclein.European journal of nuclear medicine and molecular imaging · 2024Article
- Small Molecules, α-Synuclein Pathology, and the Search for Effective Treatments in Parkinson's Disease.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggregation of amyloidogenic proteins is a characteristic of multiple neurodegenerative diseases. Atomic resolution of small molecule binding to such pathological protein aggregates is of interest for the development of therapeutics and diagnostics. Here we investigate the interaction between α-synuclein fibrils and anle138b, a clinical drug candidate for disease modifying therapy in neurodegeneration and a promising scaffold for positron emission tomography tracer design. We used nuclear magnetic resonance spectroscopy and the cryogenic electron microscopy structure of α-synuclein fibrils grown in the presence of lipids to locate anle138b within a cavity formed between two β-strands. We explored and quantified multiple binding modes of the compound in detail using molecular dynamics simulations. Our results reveal stable polar interactions between anle138b and backbone moieties inside the tubular cavity of the fibrils. Such cavities are common in other fibril structures as well.
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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.