A novel human model of the neurodegenerative disease GM1 gangliosidosis using induced pluripotent stem cells demonstrates inflammasome activation. Issue 1 (26th May 2015)

• Record Type: Journal Article
• Authors: Son, Mi‐Young; Kwak, Jae Eun; Seol, Binna; Lee, Da Yong; Jeon, Hyejin; Cho, Yee Sook
• Is Part Of: Journal of pathology. Volume 237:Issue 1(2015)
• Page Start: 98
• Page End: 110
• Publication Date: 2015-05-26
• Subjects: Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.4551
• Languages: English
• ISSNs: 0022-3417

Abstract

<abstract abstract-type="main" id="path4551-abs-0001"> <title>Abstract</title> <p id="path4551-para-0001">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 <italic>in vitro</italic> 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 <italic>in vitro</italic> and <italic>in vivo</italic>. Our data demonstrate that GM1‐NPCs are a valuable <italic>in vitro</italic> 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. Published by John Wiley &amp; Sons, Ltd.</p> </abstract>