Awakening the dark side: retrotransposon activation in neurodegenerative disorders.
Elizabeth Ochoa Thomas, Gabbe Zuniga, Wenyan Sun, Bess Frost.
Current Opinion in Neurobiology. 2020 Apr;61:65-72. doi: 10.1016/j.conb.2020.01.012. Epub 2020 Feb 21.
Nearly half (45%) of the human genome is composed of transposable elements, or ‘jumping genes’. Since Barbara McClintock’s original discovery of transposable elements in 1950, we have come to appreciate that transposable element mobilization is a major driver of evolution that transposons are active in the germline and the soma, and that transposable element dysregulation is causally associated with many human disorders. In the present review, we highlight recent studies investigating transposable element activation in the adult brain and in the context of neurodegeneration. Collectively, these studies contribute to a greater understanding of the frequency of complete retrotransposition in the adult brain as well as the presence of transposable element-derived RNA and protein in brain and fluids of patients with neurodegenerative disorders. We discuss therapeutic opportunities and speculate on the larger implications of transposable element activation in regard to current hot topics in the field of neurodegeneration.