ArticleHuman molecular genetics2018
The c-Abl inhibitor, Radotinib HCl, is neuroprotective in a preclinical Parkinson's disease mouse model.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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The trial behind it
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Who cites it
53 citing papers in PubMed, 83 citations in OpenAlex.
- The 201 Trial: a placebo-controlled randomized phase 2 study of safety and tolerance of the c-Abl kinase inhibitor risvodetinib in untreated Parkinson's disease.Nature aging · 2026Trial
- Considerations for therapeutic targets for clinical trials in biomarker-characterized prodromal Parkinson's disease populations.Journal of Parkinson's disease · 2026Article
- Neuronal titration of Snca via enhancer disruption mitigates disease onset in a Parkinson's disease mouse model.Brain : a journal of neurology · 2026Article
- Emerging New Pathways in Malignant Neoplasms and Neurodegenerative Disorders: Perspectives for Therapeutics.Cells · 2026Review
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Computational Repurposing of Nilotinib and Radotinib as SIRT2 Inhibitors for Neurodegenerative Diseases.Journal of molecular neuroscience : MN · 2026Article
- Evaluation of c-Abl inhibitor vodobatinib in subjects with early Parkinson's disease: a phase 2, randomized, double-blind, placebo-controlled study.NPJ Parkinson's disease · 2026Article
- Fluorescence Lifetime-Based FRET Biosensors for Monitoring N Terminal Domain-Dependent Interactions of TDP-43 in Living Cells: A Novel Approach for ALS and FTD Drug Discovery.ACS chemical neuroscience · 2025Article
- c-Abl Inhibitors in Parkinson's: Exploring Hypotheses on Alpha-Synuclein Modulation.Advanced pharmaceutical bulletin · 2025Article
- An Integrative Computational Approach for the Identification of C-Abl Kinase Inhibitors from Anti-Parkinson Plant-Derived Bioactive.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Article
- α-Synuclein pathology as a target in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- An update on novel and emerging therapeutic targets in Parkinson's disease.Metabolic brain disease · 2024Review
- Neuroprotective Activity of a Non-Covalent Imatinib+TP10 Conjugate in HT-22 Neuronal Cells In Vitro.Pharmaceutics · 2024Article
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
- Glutamate Receptors and C-ABL Inhibitors: A New Therapeutic Approach for Parkinson's Disease.Central nervous system agents in medicinal chemistry · 2024Review
- c-Abl Phosphorylates MFN2 to Regulate Mitochondrial Morphology in Cells under Endoplasmic Reticulum and Oxidative Stress, Impacting Cell Survival and Neurodegeneration.Antioxidants (Basel, Switzerland) · 2023Article
- α-Synuclein oligomers and fibrils: partners in crime in synucleinopathies.Neural regeneration research · 2023Article
- Review
- Radotinib Decreases Prion Propagation and Prolongs Survival Times in Models of Prion Disease.International journal of molecular sciences · 2023Article
- Targeting the Cysteine Redox Proteome in Parkinson's Disease: The Role of Glutathione Precursors and Beyond.Antioxidants (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Accumulating evidence suggests that the non-receptor tyrosine kinase c-Abl plays an important role in the progression of Parkinson's disease (PD) and c-Abl inhibition could be neuroprotective in PD and related α-synucleinopathies. Nilotinib, a c-Abl inhibitor, has shown improved motor and cognitive symptoms in PD patients. However, issues concerning blood-brain barrier (BBB) penetration, lack of selectivity and safety still remain. Radotinib HCl is a selective Bcr-Abl kinase inhibitor that not only effectively access the brain, but also exhibits greater pharmacokinetic properties and safety profiles compared to Nilotinib and other c-Abl inhibitors. Here, we show the neuroprotective efficacy of Radotinib HCl, a brain penetrant c-Abl inhibitor, in a pre-clinical model of PD. Importantly, in vitro studies demonstrate that the treatment of Radotinib HCl protects the α-synuclein preformed fibrils (PFF)-induced neuronal toxicity, reduces the α-synuclein PFF-induced Lewy bodies (LB)/Lewy neurites (LN)-like pathology and inhibits the α-synuclein PFF-induced c-Abl activation in primary cortical neurons. Furthermore, administration of Radotinib HCl inhibits c-Abl activation and prevents dopaminergic neuron loss, neuroinflammation and behavioral deficits following α-synuclein PFF-induced toxicity in vivo. Taken together, our findings indicate that Radotinib HCl has beneficial neuroprotective effects in PD and provides an evidence that selective and brain permeable c-Abl inhibitors can be potential therapeutic agents for the treatment of PD and related α-synucleinopathies.
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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.