한빛사 논문
Markus Riessland,1,7,10,* Benjamin Kolisnyk,1,7 Tae Wan Kim,2,3,7 Jia Cheng,1 Jason Ni,1 Jordan A. Pearson,1 Emily J. Park,1 Kevin Dam,1 Devrim Acehan,4 Lavoisier S. Ramos-Espiritu,5 Wei Wang,1 Jack Zhang,1 Jae-won Shim,6 Gabriele Ciceri,2,3 Lars Brichta,1 Lorenz Studer,2,3,8,* and Paul Greengard1,8,9
1 Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA
2 Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, USA
3 Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, USA
4 Electron Microscopy Resource Center, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA
5 High-Throughput and Spectroscopy Resource Center, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA
6 Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Korea
7 These authors contributed equally
8 These authors contributed equally
9 Dedicated to Paul Greengard (died April 13, 2019)
10 Lead Contact
*Correspondence: Markus Riessland, Lorenz Studer
Abstract
Cellular senescence is a mechanism used by mitotic cells to prevent uncontrolled cell division. As senescent cells persist in tissues, they cause local inflammation and are harmful to surrounding cells, contributing to aging. Generally, neurodegenerative diseases, such as Parkinson’s, are disorders of aging. The contribution of cellular senescence to neurodegeneration is still unclear. SATB1 is a DNA binding protein associated with Parkinson’s disease. We report that SATB1 prevents cellular senescence in post-mitotic dopaminergic neurons. Loss of SATB1 causes activation of a cellular senescence transcriptional program in dopamine neurons both in human stem cell-derived dopaminergic neurons and in mice. We observed phenotypes that are central to cellular senescence in SATB1 knockout dopamine neurons in vitro and in vivo. Moreover, we found that SATB1 directly represses expression of the pro-senescence factor p21 in dopaminergic neurons. Our data implicate senescence of dopamine neurons as a contributing factor in the pathology of Parkinson’s disease.
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