%0 Journal Article %J J Alzheimers Dis %D 2018 %T DJ-1 Suppresses Cytoplasmic TDP-43 Aggregation in Oxidative Stress-Induced Cell Injury. %A Lei, Yang %A Zhang, Zhi-Feng %A Lei, Rui-Xue %A Wang, Shu %A Zhuang, Yang %A Liu, An-Chun %A Wu, Yan %A Chen, Juan %A Tang, Jun-Chun %A Pan, Meng-Xian %A Liu, Rui %A Liao, Wei-Jing %A Feng, Yu-Gong %A Wan, Qi %A Zheng, Mei %X

DJ-1 (also called PARK7) is a multifunctional redox-sensitive protein that is protective against oxidative stress-induced cell death. TAR DNA-binding protein 43 (TDP-43) is a major protein component of pathological inclusions in amyotrophic lateral sclerosis and frontotemporal dementia. Reducing aberrant aggregation of TDP-43 is a potential approach to prevent cell death. To investigate whether DJ-1 might inhibit TDP-43 aggregation to exert a protective effect in oxidative stress-induced injury, we tested the protein level and subcellular localization of TDP-43 and DJ-1 in SH-SY5Y cells transfected with wild-type DJ-1, DJ-1 mutant (L166P) cDNA, or DJ-1 siRNA. We show that oxidative stress induced by paraquat leads to the formation of cytosolic TDP-43 aggregation in SH-SY5Y cells. DJ-1 overexpression decreases paraquat-induced cytoplasmic accumulation of TDP-43 in SH-SY5Y cells and protects against paraquat-induced cell death. Transfection of DJ-1 L166P mutant or DJ-1 siRNA leads to increased cytosolic aggregation of TDP-43 in paraquat-treated SH-SY5Y cells and promotes cell death. These data suggest that DJ-1 may protect against oxidative stress-induced cell death through the suppression of cytoplasmic TDP-43 aggregation.

%B J Alzheimers Dis %V 66 %P 1001-1014 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/30372676?dopt=Abstract %R 10.3233/JAD-180460