Tracing a path towards neuronal cell death in Alexander disease

Alexander Disease
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. Image courtesy of Liqun Wang, Feany lab, Brigham & Women’s Hospital

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.

Albee Messing
Albee Messing, VMD, PhD

Researchers at Brigham and Women’s Hospital (BWH) in collaboration with Albee Messing, VMD, PhD, and Tracy Hagemann, PhD, at the Waisman Center at University of Wisconsin-Madison 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.”

To learn more about Alexander disease research at the Waisman Center, please visit