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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

Authors :
Clara Grudina
Georgia Kouroupi
Takashi Nonaka
Masato Hasegawa
Rebecca Matsas
Chiara Zurzolo
Source :
Neurobiology of Disease, Vol 132, Iss , Pp - (2019)
Publication Year :
2019
Publisher :
Elsevier, 2019.

Abstract

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.

Details

Language :
English
ISSN :
1095953X
Volume :
132
Issue :
-
Database :
Directory of Open Access Journals
Journal :
Neurobiology of Disease
Publication Type :
Academic Journal
Accession number :
edsdoj.b5429555a6b94eadb2f0edc6d765e084
Document Type :
article
Full Text :
https://doi.org/10.1016/j.nbd.2019.104609