ArticleNPJ Parkinson's disease2022
High content screening and proteomic analysis identify a kinase inhibitor that rescues pathological phenotypes in a patient-derived model of Parkinson's disease.
Article in NPJ Parkinson's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Elucidating the role of DEAF1 in neurodevelopment and shared molecular pathways in high-risk autism genes using cortical organoids.Science advances · 2026Article
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- From mice to clinical relevance: humanizing neuroscience with human-based model systems.Frontiers in cellular neuroscience · 2026Review
- Dysregulated proteostasis in p.A53T-α-Synuclein astrocytes aggravates Lewy-like neuropathology in a Parkinson's disease iPSC model.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The rise of neural stem cells: From development to disease.Stem cell reports · 2025Article
- Unique nigral and cortical pathways implicated by epigenomic and transcriptional analyses in rotenone Parkinson's model.NPJ Parkinson's disease · 2025Article
- Article
- A comprehensive update on the application of high-throughput fluorescence imaging for novel drug discovery.Expert opinion on drug discovery · 2025Review
- Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.Journal of neuroinflammation · 2025Review
- Proteomic insights into the biology of dopaminergic neurons.Frontiers in molecular neuroscience · 2025Review
- Clinical translation of human iPSC technologies: advances, safety concerns, and future directions.Frontiers in cell and developmental biology · 2025Review
- Systematic identification of structure-specific protein-protein interactions.Molecular systems biology · 2024Article
- ATM-mediated co-chaperone DNAJB11 phosphorylation facilitates α-synuclein folding upon DNA double-stranded breaks.NAR molecular medicine · 2024Article
- Proteomic Changes in the Hippocampus after Repeated Explosive-Driven Blasts.Journal of proteome research · 2024Article
- Proteomic changes in the hippocampus of large mammals after total-body low dose radiation.PloS one · 2024Article
- Pluripotent Stem Cell-derived Dopaminergic Neurons for Studying Developmental Neurotoxicity.Stem cell reviews and reports · 2023Review
- Recent Advances in High-Content Imaging and Analysis in iPSC-Based Modelling of Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Variation in Exon 29 of the NOS1 Gene Does Not Contribute to Parkinson's Disease in the North Karnataka Population.Cureus · 2023Article
- AZD5438 a GSK-3a/b and CDK inhibitor is antiapoptotic modulates mitochondrial activity and protects human neurons from mitochondrial toxins.Scientific reports · 2023Article
- Rapid and Robust Multi-Phenotypic Assay System for ALS Using Human iPS Cells with Mutations in Causative Genes.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Combining high throughput screening approaches with induced pluripotent stem cell (iPSC)-based disease modeling represents a promising unbiased strategy to identify therapies for neurodegenerative disorders. Here we applied high content imaging on iPSC-derived neurons from patients with familial Parkinson's disease bearing the G209A (p.A53T) α-synuclein (αSyn) mutation and launched a screening campaign on a small kinase inhibitor library. We thus identified the multi-kinase inhibitor BX795 that at a single dose effectively restores disease-associated neurodegenerative phenotypes. Proteomics profiling mapped the molecular pathways underlying the protective effects of BX795, comprising a cohort of 118 protein-mediators of the core biological processes of RNA metabolism, protein synthesis, modification and clearance, and stress response, all linked to the mTORC1 signaling hub. In agreement, expression of human p.A53T-αSyn in neuronal cells affected key components of the mTORC1 pathway resulting in aberrant protein synthesis that was restored in the presence of BX795 with concurrent facilitation of autophagy. Taken together, we have identified a promising small molecule with neuroprotective actions as candidate therapeutic for PD and other protein conformational disorders.
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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.