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© Research
Publication : Neurobiology of disease

Human NPCs can degrade α-syn fibrils and transfer them preferentially in a cell contact-dependent manner possibly through TNT-like structures.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Neurobiology of disease - 01 Dec 2019

Grudina C, Kouroupi G, Nonaka T, Hasegawa M, Matsas R, Zurzolo C,

Link to Pubmed [PMID] – 31494284

Link to DOI [DOI] – S0969-9961(19)30284-010.1016/j.nbd.2019.104609

Neurobiol Dis 2019 12; 132(): 104609

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.

https://pubmed.ncbi.nlm.nih.gov/31494284