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Archive - Dec 25, 2018


Neurite Shrinking in Aging Mice Is Related to Mitochondria Dysfunction Caused by Problems with Protein Supply Chain at Ends of Neurites; Huntington’s Disease Protein Interferes with Same Supply Chain and Causes HD-Similar Disease in Mice

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.

Support for Exaggerated Immune Response As Possible Trigger for Chronic Fatigue Syndrome

New research from King’s College London finds that an exaggerated immune response can trigger long-lasting fatigue, potentially explaining how chronic fatigue syndrome (CFS) begins. The study is the most in-depth biological investigation yet into the role of the immune system in lasting symptoms of fatigue. CFS, also known as myalgic encephalomyelitis (ME), is a long-term illness which is characterized by extreme tiredness. The underlying biology of CFS has remained a mystery, hampering the search for treatments. There is some evidence that the immune system plays a role in triggering CFS and many patients report their illness starting with a challenge to the immune system such as a viral illness. By the time patients are diagnosed, it is too late to catch CFS in its earliest stages, and it is impossible to assess the biology of patients before the illness develops. To get around this problem, researchers from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) used a model for CFS based on a treatment for hepatitis C called interferon-alpha. Interferon-alpha activates the immune system in the same way as a powerful infection. A lot of patients develop acute fatigue during treatment with interferon-alpha and a minority go on to have a CFS-like illness, where fatigue lasts for more than six months after the treatment ends. The researchers measured fatigue and immune system markers in 55 patients before, during, and after treatment with interferon-alpha, tracking which people developed the persistent CFS-like illness. The team found differences in the immune systems of 18 patients who developed lasting fatigue compared to those who recovered as normal.