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Tau-Induced Neurodegeneration Associated with Global Relaxation of Tightly-Wound DNA in Alzheimer’s Disease

In a study published online on January 26, 2014 in Nature Neuroscience, Bess Frost, Ph.D., from the Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, and co-authors, identify abnormal expression of genes, resulting from DNA relaxation, that can be detected in the brain and blood of Alzheimer's patients. The protein tau (image) is involved in a number of neurodegenerative disorders, including Alzheimer's disease. Previous studies have implicated DNA damage as a cause of neuron, or cell, death in Alzheimer's patients. Given that DNA damage can change the structure of DNA within cells, the researchers examined changes in DNA structure in tau-induced neurodegeneration. They used transgenic flies and mice expressing human tau to show that DNA is more relaxed in tauopathy. They then identified that the relaxation of tightly wound DNA and resulting abnormal gene expression are central events that cause neurons to die in Alzheimer's disease. The authors write, "Our work suggests that drugs that modify DNA structure may be beneficial for treating Alzheimer's Disease." The authors recommend, "A greater understanding of the pathway of DNA relaxation in tauopathies will allow us to identify the optimal target and explore the therapeutic potential of epigenetic-based drugs." The title of their article is, “Tau Promotes Neurodegeneration through Global Chromatin Relaxation.” [Press release] [Nature Neuroscience abstract]