Cap, Kim Cuong Jung, Yeon-Joo Choi, Bo Young Hyeon, Seung Jae Kim, Jae-Gyu Min, Jung-Ki Islam, Rokibul Hossain, Abu Jubayer Chung, Won-Suk Suh, Sang Won Ryu, Hoon Park, Jae-Bong 2024-01-19T17:33:22Z 2024-01-19T17:33:22Z 2021-09-05 2020-05 2213-2317 https://pubs.kist.re.kr/handle/201004/118665 Both the accumulation of Amyloid-beta (A beta) in plaques and phosphorylation of Tau protein (p-Tau) in neurofibrillary tangles have been identified as two major symptomatic features of Alzheimer's disease (AD). Despite of critical role of A beta and p-Tau in AD progress, the interconnection of signalling pathways that A beta induces p-Tau remains elusive. Herein, we observed that a popular AD model mouse (APP/PS1) and A beta-injected mouse showed an increase in p-Tyr42 Rho in hippocampus of brain. Low concentrations of A beta (1 mu M) induced RhoA-mediated Ser422 phosphorylation of Tau protein (p-Ser422 Tau), but reduced the expression of ATP citrate lyase (ACL) in the HT22 hippocampal neuronal cell line. In contrast, high concentrations of A beta (10 mu M) along with high levels of superoxide production remarkably attenuated accumulation of p-Ser422 Tau, but augmented ACL expression and activated sterol regulatory element-binding protein 1 (SREBP1), leading to cellular senescence. Notably, a high concentration of A beta(10 mu M) induced nuclear localization of p-Tyr42 Rho, which positively regulated NAD kinase (NADK) expression by binding to the NADK promoter. Furthermore, severe AD patient brain showed high p-Tyr42 Rho levels. Collectively, our findings indicate that both high and low concentrations of A beta are detrimental to neurons via distinct two p-Tyr42 RhoA-mediated signalling pathways in Ser422 phosphorylation of Tau and ACL expression. English ELSEVIER NEURITE OUTGROWTH NADPH OXIDASE MITOCHONDRIAL SUPEROXIDE MOUSE MODEL CELLS INACTIVATION ACCUMULATION P190RHOGAP SENESCENCE PATHWAY Distinct dual roles of p-Tyr42 RhoA GTPase in tau phosphorylation and ATP citrate lyase activation upon different A beta concentrations Article 10.1016/j.redox.2020.101446 1 REDOX BIOLOGY, v.32 REDOX BIOLOGY 32 scie scopus 000537459900032 2-s2.0-85079048470 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article NEURITE OUTGROWTH NADPH OXIDASE MITOCHONDRIAL SUPEROXIDE MOUSE MODEL CELLS INACTIVATION ACCUMULATION P190RHOGAP SENESCENCE PATHWAY ACL Alzheimer disease A beta NADK Superoxide p-Tyr42 RhoA p-Tau