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Human NPCs can degrade α–syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures
- Source :
- Neurobiology of Disease, Vol 132, Iss, Pp-(2019), Neurobiology of Disease, Neurobiology of Disease, Elsevier, 2019, 132, pp.104609. ⟨10.1016/j.nbd.2019.104609⟩, Neurobiology of Disease, 2019, 132, pp.104609. ⟨10.1016/j.nbd.2019.104609⟩
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 09699961 and 1095953X
- Volume :
- 132
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Disease
- Accession number :
- edsair.doi.dedup.....554e44cfa10bd69ff69f5e7f88cbbe22