RT Journal Article
SR Electronic
T1 The inhibition of LSD1 via sequestration contributes to tau-mediated neurodegeneration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 745133
DO 10.1101/745133
A1 Amanda K. Engstrom
A1 Alicia C. Walker
A1 Rohitha A. Moudgal
A1 Dexter A. Myrick
A1 Stephanie M. Kyle
A1 David J. Katz
YR 2020
UL http://biorxiv.org/content/early/2020/02/11/745133.abstract
AB Tauopathies are a class of neurodegenerative diseases associated with pathological tau. However, the mechanism through which tau contributes to neurodegeneration remains unknown. Previously, our lab implicated the histone demethylase LSD1 in tau-induced neurodegeneration by showing that LSD1 localizes to pathological tau aggregates in Alzheimer’s disease cases, and that it is continuously required for the survival of hippocampal and cortical neurons in mice. Here, we utilize the P301S tauopathy mouse model to demonstrate that pathological tau can exclude LSD1 from the nucleus in neurons. In addition, we show that reducing LSD1 in these mice is sufficient to highly exacerbate tau-mediated neurodegeneration. Finally, we find that overexpressing LSD1 in the hippocampus of tauopathy mice, even after pathology has formed, is sufficient to significantly delay neurodegeneration. These results suggest that inhibiting LSD1 via sequestration contributes to tau-mediated neurodegeneration. Thus, LSD1 is a promising therapeutic target for tauopathies such as Alzheimer’s disease.