ArticleHuman molecular genetics2018
In silico drug screening by using genome-wide association study data repurposed dabrafenib, an anti-melanoma drug, for Parkinson's disease.
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 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
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- Prioritizing Parkinson's disease risk genes in genome-wide association loci.NPJ Parkinson's disease · 2025Article
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- Alzheimer's disease and its treatment-yesterday, today, and tomorrow.Frontiers in pharmacology · 2024Review
- OncogenicNeural regeneration research · 2023Article
- The small GTPase Rit2 modulates LRRK2 kinase activity, is required for lysosomal function and protects against alpha-synuclein neuropathology.NPJ Parkinson's disease · 2023Article
- Analyzing the ER stress response in ALS patient derived motor neurons identifies druggable neuroprotective targets.Frontiers in cellular neuroscience · 2023Article
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Repositioning of drugs for Parkinson's disease and pharmaceutical nanotechnology tools for their optimization.Journal of nanobiotechnology · 2022Review
- Necroptosis in CNS diseases: Focus on astrocytes.Frontiers in aging neuroscience · 2022Review
- Drug repurposing strategies of relevance for Parkinson's disease.Pharmacology research & perspectives · 2021Review
- Cascading from SARS-CoV-2 to Parkinson's Disease through Protein-Protein Interactions.Viruses · 2021Article
- An omics perspective on drug target discovery platforms.Briefings in bioinformatics · 2020Article
- BRAF inhibition protects against hearing loss in mice.Science advances · 2020Article
- Using functional genomics to advance the understanding of psoriatic arthritis.Rheumatology (Oxford, England) · 2020Review
- Conditional, inducible gene silencing in dopamine neurons reveals a sex-specific role for Rit2 GTPase in acute cocaine response and striatal function.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Drug Development for Central Nervous System Diseases Using In vitro Blood-brain Barrier Models and Drug Repositioning.Current pharmaceutical design · 2020Review
- Assessing drug response in engineered brain microenvironments.Brain research bulletin · 2019Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss. At present, there are no drugs that stop the progression of PD. As with other multifactorial genetic disorders, genome-wide association studies (GWASs) found multiple risk loci for PD, although their clinical significance remains uncertain. Here, we report the identification of candidate drugs for PD by a method using GWAS data and in silico databases. We identified 57 Food and Drug Administration-approved drug families as candidate neuroprotective drugs for PD. Among them, dabrafenib, which is known as a B-Raf kinase inhibitor and is approved for the treatment of malignant melanoma, showed remarkable cytoprotective effects in neurotoxin-treated SH-SY5Y cells and mice. Dabrafenib was found to inhibit apoptosis, and to enhance the phosphorylation of extracellular signal-regulated kinase (ERK), and inhibit the phosphorylation of c-Jun NH2-terminal kinase. Dabrafenib targets B-Raf, and we confirmed a protein-protein interaction between B-Raf and Rit2, which is coded by RIT2, a PD risk gene in Asians and Caucasians. In RIT2-knockout cells, the phosphorylation of ERK was reduced, and dabrafenib treatment improved the ERK phosphorylation. These data indicated that dabrafenib exerts protective effects against neurotoxicity associated with PD. By using animal model, we confirmed the effectiveness of this in silico screening method. Furthermore, our results suggest that this in silico drug screening system is useful in not only neurodegenerative diseases but also other common diseases such as diabetes mellitus and hypertension.
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