To test the hunch, Dr. Friedlander's team used genetically modified mice that carried a mutant version of the human huntingtin protein. These mice exhibit symptoms of the disease, including accelerated neuronal death. Their findings were similar to what they had seen in the cells, but more pronounced. There were fewer mitochondria at the ends, and what remained was more dysfunctional than in normal neurons. There was also more activation of caspases, and increased levels of cell death. A hallmark of neurodegenerative diseases like Huntington's is the progressive death of nerve cells in the brain. The cells don't die quickly, though. They first start to disconnect from each other because their neurites -- long finger-like extensions that make connections all through the brain -- become smaller. Now, using animal models and nerve cells grown in the lab, researchers from the University of Pittsburgh (Pitt) School of Medicine suggest a new mechanism dubbed "neuritosis" that might explain neurons shrinking in Huntington's and other neurodegenerative diseases, opening new targets for therapy. The study was published online on December 24, 2018 in PNAS. The article is titled “Mitochondria Modulate Programmed Neuritic Retraction.” Neuritosis is a process that hasn't been recognized or described until now and could play a very important role in normal brain development, aging, and neurodegenerative disease," said senior author Robert Friedlander, MD, Chair and Walter E. Dandy Professor of Neurosurgery and Neurobiology at Pitt's School of Medicine. It all started when Sergei Baranov, PhD, a staff scientist in Dr. Friedlander's lab, noticed an interesting phenomenon in mouse nerve cells that he was growing in the lab. "Their mitochondria, the cellular powerhouses, weren't working as well at the neurite ends" said Dr. Baranov.
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