Human NPCs can degrade α–syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures
Parkinson's disease (PD) is the second most common neurodegenerative disorder whereby loss of midbrain dopaminergic neurons results in motor dysfunction. Transplantation of human induced pluripotent stem cells (iPSCs) into the brain of patients affected by PD is one of the therapeutic approache...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996119302840 |
| _version_ | 1818863480629886976 |
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| author | Clara Grudina Georgia Kouroupi Takashi Nonaka Masato Hasegawa Rebecca Matsas Chiara Zurzolo |
| author_facet | Clara Grudina Georgia Kouroupi Takashi Nonaka Masato Hasegawa Rebecca Matsas Chiara Zurzolo |
| author_sort | Clara Grudina |
| collection | DOAJ |
| description | Parkinson's disease (PD) is the second most common neurodegenerative disorder whereby loss of midbrain dopaminergic neurons results in motor dysfunction. Transplantation of human induced pluripotent stem cells (iPSCs) into the brain of patients affected by PD is one of the therapeutic approaches that has gained interest to compensate for the degeneration of neurons and improve disease symptoms. However, only a part of transplanted cells can differentiate into mature neurons while the majority remains in undifferentiated state. Here we investigated whether human neuronal precursor cells (hNPCs) derived from iPSCs have an active role in α-synuclein (α-syn) pathology. Our findings demonstrate that α-syn fibrils are taken up by hNPCs and are preferentially localized in lysosomes where they can be degraded. However, α-syn fibrils are also transferred between hNPCs in a cell-to-cell contact dependent manner, and are found in tunneling nanotube (TNT)-like structures. Thus, NPCs can have a dual role in the progression of α-syn pathology, which should be considered in human transplants. |
| first_indexed | 2024-12-19T10:16:26Z |
| format | Article |
| id | doaj.art-b5429555a6b94eadb2f0edc6d765e084 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-19T10:16:26Z |
| publishDate | 2019-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-b5429555a6b94eadb2f0edc6d765e0842022-12-21T20:26:13ZengElsevierNeurobiology of Disease1095-953X2019-12-01132Human NPCs can degrade α–syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structuresClara Grudina0Georgia Kouroupi1Takashi Nonaka2Masato Hasegawa3Rebecca Matsas4Chiara Zurzolo5Unité de Traffic Membranaire et Pathogénèse, Institut Pasteur, 28 Rue du Dr. Roux, Paris 75015, FranceLaboratory of Cell and Molecular Neurobiology – Stem Cells, Department of Neurobiology, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, Athens 11521, GreeceDementia Research Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, JapanDementia Research Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, JapanLaboratory of Cell and Molecular Neurobiology – Stem Cells, Department of Neurobiology, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, Athens 11521, GreeceUnité de Traffic Membranaire et Pathogénèse, Institut Pasteur, 28 Rue du Dr. Roux, Paris 75015, France; Corresponding author.Parkinson's disease (PD) is the second most common neurodegenerative disorder whereby loss of midbrain dopaminergic neurons results in motor dysfunction. Transplantation of human induced pluripotent stem cells (iPSCs) into the brain of patients affected by PD is one of the therapeutic approaches that has gained interest to compensate for the degeneration of neurons and improve disease symptoms. However, only a part of transplanted cells can differentiate into mature neurons while the majority remains in undifferentiated state. Here we investigated whether human neuronal precursor cells (hNPCs) derived from iPSCs have an active role in α-synuclein (α-syn) pathology. Our findings demonstrate that α-syn fibrils are taken up by hNPCs and are preferentially localized in lysosomes where they can be degraded. However, α-syn fibrils are also transferred between hNPCs in a cell-to-cell contact dependent manner, and are found in tunneling nanotube (TNT)-like structures. Thus, NPCs can have a dual role in the progression of α-syn pathology, which should be considered in human transplants.http://www.sciencedirect.com/science/article/pii/S0969996119302840Parkinson's diseaseHuman neuronal precursorsAlpha-synucleinLysosomesTNT-like structures |
| spellingShingle | Clara Grudina Georgia Kouroupi Takashi Nonaka Masato Hasegawa Rebecca Matsas Chiara Zurzolo Human NPCs can degrade α–syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures Neurobiology of Disease Parkinson's disease Human neuronal precursors Alpha-synuclein Lysosomes TNT-like structures |
| title | Human NPCs can degrade α–syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures |
| title_full | Human NPCs can degrade α–syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures |
| title_fullStr | Human NPCs can degrade α–syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures |
| title_full_unstemmed | Human NPCs can degrade α–syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures |
| title_short | Human NPCs can degrade α–syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures |
| title_sort | human npcs can degrade α syn fibrils and transfer them preferentially in a cell contact dependent manner possibly through tnt like structures |
| topic | Parkinson's disease Human neuronal precursors Alpha-synuclein Lysosomes TNT-like structures |
| url | http://www.sciencedirect.com/science/article/pii/S0969996119302840 |
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