The Gypsy Endogenous Retrovirus Drives Non-Cell-Autonomous Propagation in a Drosophila TDP-43 Model of Neurodegeneration
Year: 2019
Type: article
Abstract: A hallmark of neurodegenerative disease is focal onset of pathological protein aggregation, followed by progressive spread of pathology to connected brain regions. In amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), pathology is often associated with aggregation of TAR DNA-binding protein 43 (TDP-43). Although aggregated TDP-43 protein moves between cells, it is not clear whether and how this movement propagates the degeneration. Here, we have established a Drosophila model of human TDP-43 in which we initiated toxic expression of human TDP-43 focally within small groups of glial cells. We found that this focal onset kills adjacent neurons. Surprisingly, we show that this spreading death is caused by an endogenous retrovirus within the glia, which leads to DNA damage and death in adjacent neurons. These findings suggest a possible mechanism by which human retroviruses such as HERV-K might contribute to TDP-43-mediated propagation of neurodegeneration.
Source: Current Biology
Authors: Yung-Heng Chang, Josh Dubnau
Institutions: Stony Brook School, Stony Brook Medicine, Stony Brook University
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,200
Awards: Neuronal reward mechanisms., Loss of siRNA based gene silencing and retrotransposon activation in TDP-43 mediated neurodegeneration, A systems approach to uncover upstream activators and common downstream pathways of neurodegeneration in a Drosophila model, G3254609454, Neuronal mechanisms for social information processing., Neuronal processing of risky rewards, G532636635, Neuronal reward mechanisms
OpenAlex ID: W2972083388