ArticleJournal of the American Chemical Society2024
Inhibitor Development for α-Synuclein Fibril's Disordered Region to Alleviate Parkinson's Disease Pathology.
Article in Journal of the American Chemical Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed.
- Deep Learning Assisted Heteroporous Covalent Organic Framework Hydrogels Enable Dual-Mode Tracking and Analysis to Parkinson's Management.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Engineered neuronal exosomes mediate α-synuclein clearance to ameliorate Parkinson's disease.Journal of nanobiotechnology · 2026Article
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Characterization and evaluation of the ability of graphene quantum dots to affect α-synuclein aggregation in synucleinopathy models.Science and technology of advanced materials · 2026Article
- AI-Guided Dual Strategy for Peptide Inhibitor Design Targeting Structural Polymorphs of α-Synuclein Fibrils.Cells · 2025Article
- Modulation of Aging Diseases via RAGE Targets: A Dietary Intervention Review.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Inhibition of the HMGB1-RAGE Axis Attenuates Microglial Inflammation and Ameliorates Hypoxia-Induced Cognitive Impairment.International journal of molecular sciences · 2025Article
- A New Driver of Parkinson's Disease: FAM171A2 Facilitates α-Synuclein Uptake and Spread.Neuroscience bulletin · 2025Article
- The evolving role of solid state nuclear magnetic resonance methods in studies of amyloid fibrils.Current opinion in structural biology · 2025Review
- UPLC-MS/MS Method for Givinostat in Rat Plasma: Development, Validation, in vivo Pharmacokinetics Study and in vitro Metabolic Stability Research.Drug design, development and therapy · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid fibrils of α-synuclein (α-syn) are crucial in the pathology of Parkinson's disease (PD), with the intrinsically disordered region (IDR) of its C-terminal playing a key role in interacting with receptors like LAG3 and RAGE, facilitating pathological neuronal spread and inflammation. In this study, we identified Givinostat (GS) as an effective inhibitor that disrupts the interaction of α-syn fibrils with receptors such as LAG3 and RAGE through high-throughput screening. By exploring the structure-activity relationship and optimizing GS, we developed several lead compounds, including GSD-16-24. Utilizing solution-state and solid-state NMR, along with cryo-EM techniques, we demonstrated that GSD-16-24 binds directly to the C-terminal IDR of α-syn monomer and fibril, preventing the fibril from binding to the receptors. Furthermore, GSD-16-24 significantly inhibits the association of α-syn fibrils with membrane receptors, thereby reducing neuronal propagation and pro-inflammatory effects of α-syn fibrils. Our findings introduce a novel approach to mitigate the pathological effects of α-syn fibrils by targeting their IDR with small molecules, offering potential leads for the development of clinical drugs to treat PD.
Indexed as
Identifiers
What OpenQuestion holds
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.