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Tracing a path toward neuronal cell death

Date:
November 30, 2015
Source:
Brigham and Women's Hospital
Summary:
A new genetic model has been developed that is yielding new insights into what happens when astrocytes go awry. Damage to astrocytes -- star-shaped cells found in the brain and spinal cord -- is found in many neurodegenerative conditions, but it's been unclear exactly what role astrocyte dysfunction plays in the development of disease.
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Standard histology H&E staining of tissue from an eight-year-old Alexander disease patient. Rosenthal fibers -- the hallmark of the disease -- are shown in pink; nuclei are shown in blue.
Credit: Image courtesy of Liqun Wang, Feany lab

A fruit fly model of a rare, neurodegenerative disease is helping researchers trace the series of steps that lead to neuronal cell death. Damage to astrocytes -- star-shaped cells found in the brain and spinal cord -- is found in many neurodegenerative conditions, but it's been unclear exactly what role astrocyte dysfunction plays in the development of disease.

Researchers at Brigham and Women's Hospital (BWH) have developed a genetic model that is yielding new insights into what happens when astrocytes go awry. The research team developed a fruit fly model of Alexander disease, a neurodegenerative disease that primarily affects astrocytes, and was able to narrow in on the molecular signals leading to neuronal cell death, identifying nitric oxide (NO) as a critical mediator. The team verified their results in a mouse model and also found evidence of activation of the same pathway in samples from patients with Alexander disease.

"We're excited to be contributing to a growing area of study of how astrocytes contribute to neurodegeneration, and to have uncovered a role for NO as a neuronal cell death signaling molecule," said corresponding author Mel B. Feany, MD, PhD, a senior pathologist in the BWH Department of Pathology. "Our findings define a potential mechanism for neuronal cell death in Alexander disease and possibly other neurodegenerative diseases with astrocyte dysfunction."


Story Source:

Materials provided by Brigham and Women's Hospital. Note: Content may be edited for style and length.


Journal Reference:

  1. Liqun Wang, Tracy L. Hagemann, Hermann Kalwa, Thomas Michel, Albee Messing, Mel B. Feany. Nitric oxide mediates glial-induced neurodegeneration in Alexander disease. Nature Communications, 2015; 6: 8966 DOI: 10.1038/ncomms9966

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Brigham and Women's Hospital. "Tracing a path toward neuronal cell death." ScienceDaily. ScienceDaily, 30 November 2015. <www.sciencedaily.com/releases/2015/11/151130163430.htm>.
Brigham and Women's Hospital. (2015, November 30). Tracing a path toward neuronal cell death. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/11/151130163430.htm
Brigham and Women's Hospital. "Tracing a path toward neuronal cell death." ScienceDaily. www.sciencedaily.com/releases/2015/11/151130163430.htm (accessed May 23, 2017).

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