Mutation in common protein triggers tangles, chaos inside brain cells

Named for their star shape, these astrocytes — derived from human stem cells — show their structural protein, GFAP, in red. DNA in the cell nucleus appears blue. Courtesy of Jeffrey Jones

In a study published today, Waisman Center investigators Su-Chun Zhang, Albee Messing and colleagues point to new understandings of the broad range of effects that result from the GFAP mutation impacting astrocytes — important supporting cells which comprise 20 to 40 percent of all cells in the brain.

Cells donated by patients with Alexander disease were converted into stem cells and differentiated into astrocytes. Those astrocytes formed fibrous globs of the protein GFAP, which disturbed organelles, disrupted molecular traffic systems, and reduced myelin formation.

When the GFAP-mutated stem cells were corrected with gene editing, the looked normal.

GFAP is so common, in fact, that astrocytes are identified through its presence, Zhang says. “GFAP was a big player for some reason, but nobody knew the broad range of effects, up until today.”

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Su-Chun Zhang with lab members
Standing at center, Su-Chun Zhang, professor of neuroscience in the School of Medicine and Public Health, talks with his staff as they prepare stem-cell cultures in the Zhang’s research lab at the Waisman Center at the University of Wisconsin-Madison on March 8, 2013. Also pictured are postdoctoral students Lin Yao, at left, and Yan Liu, in background, and senior research specialist Yingnan Yin, at right. (Photo by Jeff Miller/UW-Madison)