Patient-Derived Induced Pluripotent Stem Cell-Based Models in Parkinson’s Disease for Drug Identification
Parkinson’s disease (PD) is a common progressive neurodegenerative disorder characterized by loss of striatal-projecting dopaminergic neurons of the ventral forebrain, resulting in motor and cognitive deficits. Despite extensive efforts in understanding PD pathogenesis, no disease-modifying drugs ex...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7113 |
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| author | Georgia Kouroupi Nasia Antoniou Kanella Prodromidou Era Taoufik Rebecca Matsas |
| author_facet | Georgia Kouroupi Nasia Antoniou Kanella Prodromidou Era Taoufik Rebecca Matsas |
| author_sort | Georgia Kouroupi |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a common progressive neurodegenerative disorder characterized by loss of striatal-projecting dopaminergic neurons of the ventral forebrain, resulting in motor and cognitive deficits. Despite extensive efforts in understanding PD pathogenesis, no disease-modifying drugs exist. Recent advances in cell reprogramming technologies have facilitated the generation of patient-derived models for sporadic or familial PD and the identification of early, potentially triggering, pathological phenotypes while they provide amenable systems for drug discovery. Emerging developments highlight the enhanced potential of using more sophisticated cellular systems, including neuronal and glial co-cultures as well as three-dimensional systems that better simulate the human pathophysiology. In combination with high-throughput high-content screening technologies, these approaches open new perspectives for the identification of disease-modifying compounds. In this review, we discuss current advances and the challenges ahead in the use of patient-derived induced pluripotent stem cells for drug discovery in PD. We address new concepts implicating non-neuronal cells in disease pathogenesis and highlight the necessity for functional assays, such as calcium imaging and multi-electrode array recordings, to predict drug efficacy. Finally, we argue that artificial intelligence technologies will be pivotal for analysis of the large and complex data sets obtained, becoming game-changers in the process of drug discovery. |
| first_indexed | 2024-03-10T16:01:59Z |
| format | Article |
| id | doaj.art-aa96b04609034030a158150cc5a42814 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:01:59Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aa96b04609034030a158150cc5a428142023-11-20T15:13:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119711310.3390/ijms21197113Patient-Derived Induced Pluripotent Stem Cell-Based Models in Parkinson’s Disease for Drug IdentificationGeorgia Kouroupi0Nasia Antoniou1Kanella Prodromidou2Era Taoufik3Rebecca Matsas4Laboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, 11521 Athens, GreeceLaboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, 11521 Athens, GreeceLaboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, 11521 Athens, GreeceLaboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, 11521 Athens, GreeceLaboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, 11521 Athens, GreeceParkinson’s disease (PD) is a common progressive neurodegenerative disorder characterized by loss of striatal-projecting dopaminergic neurons of the ventral forebrain, resulting in motor and cognitive deficits. Despite extensive efforts in understanding PD pathogenesis, no disease-modifying drugs exist. Recent advances in cell reprogramming technologies have facilitated the generation of patient-derived models for sporadic or familial PD and the identification of early, potentially triggering, pathological phenotypes while they provide amenable systems for drug discovery. Emerging developments highlight the enhanced potential of using more sophisticated cellular systems, including neuronal and glial co-cultures as well as three-dimensional systems that better simulate the human pathophysiology. In combination with high-throughput high-content screening technologies, these approaches open new perspectives for the identification of disease-modifying compounds. In this review, we discuss current advances and the challenges ahead in the use of patient-derived induced pluripotent stem cells for drug discovery in PD. We address new concepts implicating non-neuronal cells in disease pathogenesis and highlight the necessity for functional assays, such as calcium imaging and multi-electrode array recordings, to predict drug efficacy. Finally, we argue that artificial intelligence technologies will be pivotal for analysis of the large and complex data sets obtained, becoming game-changers in the process of drug discovery.https://www.mdpi.com/1422-0067/21/19/7113disease phenotypeshigh-content screeningchemical librariesdisease-modifying drugshiPSC-derived neuronshiPSC-based co-culture systems |
| spellingShingle | Georgia Kouroupi Nasia Antoniou Kanella Prodromidou Era Taoufik Rebecca Matsas Patient-Derived Induced Pluripotent Stem Cell-Based Models in Parkinson’s Disease for Drug Identification International Journal of Molecular Sciences disease phenotypes high-content screening chemical libraries disease-modifying drugs hiPSC-derived neurons hiPSC-based co-culture systems |
| title | Patient-Derived Induced Pluripotent Stem Cell-Based Models in Parkinson’s Disease for Drug Identification |
| title_full | Patient-Derived Induced Pluripotent Stem Cell-Based Models in Parkinson’s Disease for Drug Identification |
| title_fullStr | Patient-Derived Induced Pluripotent Stem Cell-Based Models in Parkinson’s Disease for Drug Identification |
| title_full_unstemmed | Patient-Derived Induced Pluripotent Stem Cell-Based Models in Parkinson’s Disease for Drug Identification |
| title_short | Patient-Derived Induced Pluripotent Stem Cell-Based Models in Parkinson’s Disease for Drug Identification |
| title_sort | patient derived induced pluripotent stem cell based models in parkinson s disease for drug identification |
| topic | disease phenotypes high-content screening chemical libraries disease-modifying drugs hiPSC-derived neurons hiPSC-based co-culture systems |
| url | https://www.mdpi.com/1422-0067/21/19/7113 |
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