How a single mutation can devastate cellular function

A professor of neuroscience at the University of Wisconsin-Madison has shown how a single mutation in a protein found in astrocytes reproduces fibrous globs that devastate cellular function.

By Anusorn NakdeeImage Credit: Anusorn Nakdee / Shutterstock

The globs disrupt the positioning of cellular processing units, interrupt signal and energy within the brain and hinder the formation of the nerve insulator myelin.

A pioneer in neural cell studies, Professor Su-Chun Zhang, MD, Ph.D. looked at astrocytes, which play many roles in the brain including supplying nutrients, supporting cells in the blood-brain barrier, regulating calcium ion balance and aiding insulation of nerves with myelin.

For the study, Zhang took adult cells from the families of two patients with the rare and fatal genetic condition Alexander disease and converted them into stem cells, from which he could grow astrocytes.

The astrocytes he grew displayed the hallmarks of Alexander disease, including tangles made up of a protein called glial fibrillary acidic protein (GFAP) and mitochondria that were misplaced along with other cellular processing units.

As reported in the journal Cell Reports, when Zhang used CRISPR-Cas9 gene editing to correct the stem cells, the astrocytes no longer displayed any signs of Alexander disease.

Alexander disease is itself an extremely rare condition, says Zhang, but rare diseases are important in neuroscience:

We often grow to understand a disease process through rare diseases. One mutation discovered in a family with Lou Gehrig's disease led to the discovery of the fundamental pathogenesis of ALS, and the same is true for Parkinson's and Alzheimer's."

Professor Su-Chun Zhang, Lead Author

The damage caused by GFAP seems to begin with filaments aggregating within the astrocytes and causing widespread tangles that probably trigger disruption of the organelles involved in protein production, energy processing and chemical storage:

The mitochondria, endoplasmic reticulum, and lysosomes were all distributed abnormally and that was a clue that GFAP is critical for guiding organelles to their correct locations.”

Professor Su-Chun Zhang, Lead Author

Although the findings do not have any immediate clinical implications, Zhang says the impact could be broad since GFAP is the most abundant protein in astrocytes and is altered in nearly all neurological conditions including Alzheimer's, Parkinson's, Huntington's, ALS and autism.


Sally Robertson

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.


Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Robertson, Sally. (2019, June 20). How a single mutation can devastate cellular function. News-Medical. Retrieved on December 04, 2022 from

  • MLA

    Robertson, Sally. "How a single mutation can devastate cellular function". News-Medical. 04 December 2022. <>.

  • Chicago

    Robertson, Sally. "How a single mutation can devastate cellular function". News-Medical. (accessed December 04, 2022).

  • Harvard

    Robertson, Sally. 2019. How a single mutation can devastate cellular function. News-Medical, viewed 04 December 2022,


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment