| First Author | Tao CC | Year | 2017 |
| Journal | Cell Death Differ | Volume | 24 |
| Issue | 4 | Pages | 597-614 |
| PubMed ID | 28186506 | Mgi Jnum | J:348412 |
| Mgi Id | MGI:6141619 | Doi | 10.1038/cdd.2016.161 |
| Citation | Tao CC, et al. (2017) Epigenetic regulation of HDAC1 SUMOylation as an endogenous neuroprotection against Abeta toxicity in a mouse model of Alzheimer's disease. Cell Death Differ 24(4):597-614 |
| abstractText | Amyloid-beta (Abeta) produces neurotoxicity in the brain and causes neuronal death, but the endogenous defense mechanism that is activated on Abeta insult is less well known. Here we found that acute Abeta increases the expression of PIAS1 and Mcl-1 via activation of MAPK/ERK, and Abeta induction of PIAS1 enhances HDAC1 SUMOylation in rat hippocampus. Knockdown of PIAS1 decreases endogenous HDAC1 SUMOylation and blocks Abeta induction of Mcl-1. Sumoylated HDAC1 reduces it association with CREB, increases CREB binding to the Mcl-1 promoter and mediates Abeta induction of Mcl-1 expression. Transduction of SUMO-modified lenti-HDAC1 vector to the hippocampus of APP/PS1 mice rescues spatial learning and memory deficit and long-term potentiation impairment in APP/PS1 mice. It also reduces the amount of amyloid plaque and the number of apoptotic cells in CA1 area of APP/PS1 mice. Meanwhile, HDAC1 SUMOylation decreases HDAC1 binding to the neprilysin promoter. These results together reveal an important role of HDAC1 SUMOylation as a naturally occurring defense mechanism protecting against Abeta toxicity and provide an alternative therapeutic strategy against AD. |
