Modeling Alexander Disease with Patient IPSCs Reveals Cellular and Molecular Pathology of Astrocytes

Overview

Journal Acta Neuropathol Commun

Publisher Biomed Central

Specialty Neurology

Date 2016 Jul 13

PMID 27402089

Citations 27

Authors

Takayuki Kondo

Misato Funayama

Michiyo Miyake

Kayoko Tsukita

Takumi Era

Hitoshi Osaka

Takashi Ayaki

Ryosuke Takahashi

Haruhisa Inoue

Affiliations

Soon will be listed here.

Abstract

Alexander disease is a fatal neurological illness characterized by white-matter degeneration and formation of Rosenthal fibers, which contain glial fibrillary acidic protein as astrocytic inclusion. Alexander disease is mainly caused by a gene mutation encoding glial fibrillary acidic protein, although the underlying pathomechanism remains unclear. We established induced pluripotent stem cells from Alexander disease patients, and differentiated induced pluripotent stem cells into astrocytes. Alexander disease patient astrocytes exhibited Rosenthal fiber-like structures, a key Alexander disease pathology, and increased inflammatory cytokine release compared to healthy control. These results suggested that Alexander disease astrocytes contribute to leukodystrophy and a variety of symptoms as an inflammatory source in the Alexander disease patient brain. Astrocytes, differentiated from induced pluripotent stem cells of Alexander disease, could be a cellular model for future translational medicine.

Citing Articles

Morphological Characteristics and Extracellular Matrix Abnormalities in Astrocytes Derived From iPSCs of Children With Alexander Disease.

Yi H, Zhang J, Gao K, Yan W, Chu H, Zhang J CNS Neurosci Ther. 2025; 31(1):e70240.

PMID: 39868835 PMC: 11770893. DOI: 10.1111/cns.70240.

Establishment and Use of Primary Cultured Astrocytes from Alexander Disease Model Mice.

Kubota Y, Shigetomi E, Saito K, Shinozaki Y, Kobayashi K, Tanaka M Int J Mol Sci. 2024; 25(22).

PMID: 39596168 PMC: 11595037. DOI: 10.3390/ijms252212100.

Aberrant neurodevelopment in human iPS cell-derived models of Alexander disease.

Matusova Z, Dykstra W, de Pablo Y, Zetterdahl O, Canals I, van Gelder C Glia. 2024; 73(1):57-79.

PMID: 39308436 PMC: 11660530. DOI: 10.1002/glia.24618.

Human Pluripotent Stem Cell-Derived Astrocyte Functionality Compares Favorably with Primary Rat Astrocytes.

Lendemeijer B, Unkel M, Smeenk H, Mossink B, Hijazi S, Gordillo-Sampedro S eNeuro. 2024; 11(9).

PMID: 39227152 PMC: 11404293. DOI: 10.1523/ENEURO.0148-24.2024.

hPSC-Derived Astrocytes at the Forefront of Translational Applications in Neurological Disorders.

Jovanovic V, Mesch K, Tristan C Cells. 2024; 13(11.

PMID: 38891034 PMC: 11172187. DOI: 10.3390/cells13110903.

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