ArticleActa neuropathologica communications2016
Fasudil attenuates aggregation of α-synuclein in models of Parkinson's disease.
Article in Acta neuropathologica communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.
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
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- Neurodegenerative Disease Associated Pathways in the Brains of Triple Transgenic Alzheimer's Model Mice Are Reversed Following Two Weeks of Peripheral Administration of Fasudil.International journal of molecular sciences · 2023Pooled it
- Trial
- Molecular Interplay of Small Molecules and Calcium Ions with α-Synuclein Revealed by NMR and Molecular Dynamics Simulations.ACS chemical neuroscience · 2026Article
- Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule.Science advances · 2026Article
- Neuroprotective effects of ROCK inhibition on hippocampal energy metabolism in a rat model of metabolic syndrome.Iranian journal of basic medical sciences · 2026Article
- Article
- Targeting protein disorder: the next hurdle in drug discovery.Nature reviews. Drug discovery · 2025Review
- DIRseq: a method for predicting drug-interacting residues of intrinsically disordered proteins from sequences.bioRxiv : the preprint server for biology · 2025Article
- Ensemble Docking for Intrinsically Disordered Proteins.Journal of chemical information and modeling · 2025Article
- Covalent Adducts Formed by the Androgen Receptor Transactivation Domain and Small Molecule Drugs Remain Disordered.Journal of chemical information and modeling · 2025Article
- An approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ.NPJ Parkinson's disease · 2025Article
- Evidence of α-Synuclein/Glucocerebrosidase Dual Targeting by Iminosugar Derivatives.ACS chemical neuroscience · 2025Article
- Drug Repositioning and Repurposing for Disease-Modifying Effects in Parkinson's Disease.Journal of movement disorders · 2025Article
- Fasudil inhibits α-synuclein aggregation through ROCK-inhibition-mediated mechanisms.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Involvement of RhoA/ROCK Signaling Pathway in Methamphetamine-Induced Blood-Brain Barrier Disruption.Biomolecules · 2025Article
- Ensemble docking for intrinsically disordered proteins.bioRxiv : the preprint server for biology · 2025Article
- LncRNA NEAT1, an Important Biomarker Involved in the Pathological and Physiological Processes of Parkinson's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- New insights on the regulators and inhibitors of RhoA-ROCK signalling in Parkinson's disease.Metabolic brain disease · 2025Review
- The role of amphipathic and cationic helical peptides in Parkinson's disease.Protein science : a publication of the Protein Society · 2025Review
- IDRdecoder: a machine learning approach for rational drug discovery toward intrinsically disordered regions.Frontiers in bioinformatics · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, yet disease-modifying treatments do not currently exist. Rho-associated protein kinase (ROCK) was recently described as a novel neuroprotective target in PD. Since alpha-synuclein (α-Syn) aggregation is a major hallmark in the pathogenesis of PD, we aimed to evaluate the anti-aggregative potential of pharmacological ROCK inhibition using the isoquinoline derivative Fasudil, a small molecule inhibitor already approved for clinical use in humans. Fasudil treatment significantly reduced α-Syn aggregation in vitro in a H4 cell culture model as well as in a cell-free assay. Nuclear magnetic resonance spectroscopy analysis revealed a direct binding of Fasudil to tyrosine residues Y133 and Y136 in the C-terminal region of α-Syn. Importantly, this binding was shown to be biologically relevant using site-directed mutagenesis of these residues in the cell culture model. Furthermore, we evaluated the impact of long-term Fasudil treatment on α-Syn pathology in vivo in a transgenic mouse model overexpressing human α-Syn bearing the A53T mutation (α-Syn(A53T) mice). Fasudil treatment improved motor and cognitive functions in α-Syn(A53T) mice as determined by Catwalk(TM) gait analysis and novel object recognition (NOR), without apparent side effects. Finally, immunohistochemical analysis revealed a significant reduction of α-Syn pathology in the midbrain of α-Syn(A53T) mice after Fasudil treatment. Our results demonstrate that Fasudil, next to its effects mediated by ROCK-inhibition, directly interacts with α-Syn and attenuates α-Syn pathology. This underscores the translational potential of Fasudil as a disease-modifying drug for the treatment of PD and other synucleinopathies.
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.