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Title 

A novel human model of the neurodegenerative disease GM1 gangliosidosis using induced pluripotent stem cells demonstrates inflammasome activation

Authors 

Mi Young SonJae Eun KwakBinna SeolDa Yong LeeHyejin JeonYee Sook Cho

Issue Date 

2015

Citation 

Journal of Pathology, vol. 237, no. 1, pp. 98-110

Keywords 

GM1 gangliosidosishuman disease modelinduced pluripotent stem cellsinflammasomeneural progenitor cells

Abstract 

GM1 gangliosidosis (GM1) is an inherited neurodegenerative disorder caused by mutations in the lysosomal β-galactosidase (β-gal) gene. Insufficient β-gal activity leads to abnormal accumulation of GM1 gangliosides in tissues, particularly in the central nervous system, resulting in progressive neurodegeneration. Here, we report an in vitro human GM1 model, based on induced pluripotent stem cell (iPSC) technology. Neural progenitor cells differentiated from GM1 patient-derived iPSCs (GM1-NPCs) recapitulated the biochemical and molecular phenotypes of GM1, including defective β-gal activity and increased lysosomes. Importantly, the characterization of GM1-NPCs established that GM1 is significantly associated with the activation of inflammasomes, which play a critical role in the pathogenesis of various neurodegenerative diseases. Specific inflammasome inhibitors potently alleviated the disease-related phenotypes of GM1-NPCs in vitro and in vivo. Our data demonstrate that GM1-NPCs are a valuable in vitro human GM1 model and suggest that inflammasome activation is a novel target pathway for GM1 drug development. Copyright ? 2015 Pathological Society of Great Britain and Ireland.

ISSN 

0022-3417

Link 

http://dx.doi.org/10.1002/path.4551

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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