Tracing a path toward neuronal cell death
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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."
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Wang L et al. Nitric oxide mediates glial-induced neurodegeneration in Alexander disease. Nature Communications, Published November 26 2015. doi: 10.1038/ncomms9966