1. Human NPCs can degrade α–syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures
- Author
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Masato Hasegawa, Clara Grudina, Takashi Nonaka, Rebecca Matsas, Chiara Zurzolo, Georgia Kouroupi, Trafic membranaire et Pathogénèse, Institut Pasteur [Paris], Institut Pasteur Hellénique, Réseau International des Instituts Pasteur (RIIP), Dementia Research Project, Tokyo Metropolitan Institute of Medical Science (TMIMS), This work was supported by the Programme Transversaux De Recherche - PTR (523) from Institut Pasteur (R.M. and C.Z), Agence Nationale de la Recherche [ANR-16CE-0019-01] (C.Z), Fondation pour la Recherche Médicale [FRM-2016-DEQ20160334896] (C.Z), France Alzheimer [AAP SM 2017#1674] (C.Z), LECMA-VAINCRE ALZHEIMER [2016/FR-16020] (C.Z), Scientific Research on Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) [JP14533254] [JP18dm0207019] from AMED (M.H.), JST CREST (JP18071300) (M.H.)., We are thankful to Dr. Michael Henderson for the proofread of this manuscript, all lab members of CZ group for all suggestions and technical supports in this project., ANR-16-CE16-0019,Neurotunn,Role des nanotubes membranaires dans la propagation d'agrégats protéiques impliqués dans les maladie neurodégénératives(2016), Grudina, C., Kouroupi, G., Nonaka, T., Hasegawa, M., Matsas, R., Zurzolo, C., and Institut Pasteur [Paris] (IP)
- Subjects
0301 basic medicine ,MESH: Neural Stem Cells ,Parkinson's disease ,Human neuronal precursors ,[SDV]Life Sciences [q-bio] ,Cell Communication ,Degeneration (medical) ,Induced Pluripotent Stem Cell ,chemistry.chemical_compound ,0302 clinical medicine ,Neural Stem Cells ,MESH: Dopaminergic Neurons ,Neural Stem Cell ,TNT-like structure ,Induced pluripotent stem cell ,Endocytosi ,Dopaminergic ,Lysosome ,Endocytosis ,Cell biology ,Neurology ,MESH: Endocytosis ,Dopaminergic Neuron ,Human ,Induced Pluripotent Stem Cells ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,MESH: Induced Pluripotent Stem Cells ,Fibril ,lcsh:RC321-571 ,Midbrain ,Alpha-synuclein ,03 medical and health sciences ,MESH: Cell Communication ,MESH: alpha-Synuclein ,alpha-Synuclein ,medicine ,Humans ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,MESH: Humans ,Dopaminergic Neurons ,medicine.disease ,Transplantation ,TNT-like structures ,Human neuronal precursor ,030104 developmental biology ,chemistry ,nervous system ,Lysosomes ,030217 neurology & neurosurgery ,MESH: Lysosomes - Abstract
International audience; 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.
- Published
- 2019