Matches in SemOpenAlex for { <https://semopenalex.org/work/W3207658114> ?p ?o ?g. }
- W3207658114 abstract "Abstract DNA damage is increased in Alzheimer’s disease (AD), while the underlying mechanisms are unknown. Here, we employ comprehensive phosphoproteome analysis, and identify abnormal phosphorylation of 70 kDa subunit of Ku antigen (Ku70) at Ser77/78, which prevents Ku70-DNA interaction, in human AD postmortem brains. The abnormal phosphorylation inhibits accumulation of Ku70 to the foci of DNA double strand break (DSB), impairs DNA damage repair and eventually causes transcriptional repression-induced atypical cell death (TRIAD). Cells under TRIAD necrosis reveal senescence phenotypes. Extracellular high mobility group box 1 (HMGB1) protein, which is released from necrotic or hyper-activated neurons in AD, binds to toll-like receptor 4 (TLR4) of neighboring neurons, and activates protein kinase C alpha (PKCα) that executes Ku70 phosphorylation at Ser77/78. Administration of human monoclonal anti-HMGB1 antibody to post-symptomatic AD model mice decreases neuronal DSBs, suppresses secondary TRIAD necrosis of neurons, prevents escalation of neurodegeneration, and ameliorates cognitive symptoms. TRIAD shares multiple features with senescence. These results discover the HMGB1-Ku70 axis that accounts for the increase of neuronal DNA damage and secondary enhancement of TRIAD, the cell death phenotype of senescence, in AD." @default.
- W3207658114 created "2021-10-25" @default.
- W3207658114 creator A5006054960 @default.
- W3207658114 creator A5010899579 @default.
- W3207658114 creator A5013301564 @default.
- W3207658114 creator A5015110283 @default.
- W3207658114 creator A5017563247 @default.
- W3207658114 creator A5017854980 @default.
- W3207658114 creator A5023317571 @default.
- W3207658114 creator A5024641774 @default.
- W3207658114 creator A5027331748 @default.
- W3207658114 creator A5028208584 @default.
- W3207658114 creator A5029920510 @default.
- W3207658114 creator A5038819740 @default.
- W3207658114 creator A5043599525 @default.
- W3207658114 creator A5046705010 @default.
- W3207658114 creator A5059167845 @default.
- W3207658114 creator A5063835821 @default.
- W3207658114 creator A5074475230 @default.
- W3207658114 creator A5074864226 @default.
- W3207658114 creator A5075516626 @default.
- W3207658114 creator A5082201853 @default.
- W3207658114 creator A5088884397 @default.
- W3207658114 date "2021-10-11" @default.
- W3207658114 modified "2023-10-14" @default.
- W3207658114 title "HMGB1 signaling phosphorylates Ku70 and impairs DNA damage repair in Alzheimer’s disease pathology" @default.
- W3207658114 cites W1031578623 @default.
- W3207658114 cites W1511608592 @default.
- W3207658114 cites W1536477417 @default.
- W3207658114 cites W1541957757 @default.
- W3207658114 cites W1617816798 @default.
- W3207658114 cites W1745187809 @default.
- W3207658114 cites W1895398290 @default.
- W3207658114 cites W1973309606 @default.
- W3207658114 cites W1973404097 @default.
- W3207658114 cites W1973571562 @default.
- W3207658114 cites W1975403755 @default.
- W3207658114 cites W1976276205 @default.
- W3207658114 cites W1978888457 @default.
- W3207658114 cites W1989718007 @default.
- W3207658114 cites W1991915850 @default.
- W3207658114 cites W1994190235 @default.
- W3207658114 cites W1996212779 @default.
- W3207658114 cites W2000285763 @default.
- W3207658114 cites W2003000287 @default.
- W3207658114 cites W2006764478 @default.
- W3207658114 cites W2008983065 @default.
- W3207658114 cites W2020731149 @default.
- W3207658114 cites W2021520922 @default.
- W3207658114 cites W2024303872 @default.
- W3207658114 cites W2024954534 @default.
- W3207658114 cites W2026084202 @default.
- W3207658114 cites W2039386747 @default.
- W3207658114 cites W2041186171 @default.
- W3207658114 cites W2044341880 @default.
- W3207658114 cites W2052036700 @default.
- W3207658114 cites W2054496958 @default.
- W3207658114 cites W2054538838 @default.
- W3207658114 cites W2056079743 @default.
- W3207658114 cites W2063661531 @default.
- W3207658114 cites W2073301516 @default.
- W3207658114 cites W2074343204 @default.
- W3207658114 cites W2080053685 @default.
- W3207658114 cites W2090408878 @default.
- W3207658114 cites W2090620788 @default.
- W3207658114 cites W2102414780 @default.
- W3207658114 cites W2108169752 @default.
- W3207658114 cites W2109491705 @default.
- W3207658114 cites W2113037810 @default.
- W3207658114 cites W2114108194 @default.
- W3207658114 cites W2125644182 @default.
- W3207658114 cites W2127587930 @default.
- W3207658114 cites W2127620502 @default.
- W3207658114 cites W2128367294 @default.
- W3207658114 cites W2131078803 @default.
- W3207658114 cites W2131418908 @default.
- W3207658114 cites W2132262459 @default.
- W3207658114 cites W2132959555 @default.
- W3207658114 cites W2136367337 @default.
- W3207658114 cites W2141240737 @default.
- W3207658114 cites W2143285014 @default.
- W3207658114 cites W2150594596 @default.
- W3207658114 cites W2150894667 @default.
- W3207658114 cites W2157837108 @default.
- W3207658114 cites W2159724295 @default.
- W3207658114 cites W2159882838 @default.
- W3207658114 cites W2161080185 @default.
- W3207658114 cites W2161887614 @default.
- W3207658114 cites W2162229546 @default.
- W3207658114 cites W2162412306 @default.
- W3207658114 cites W2162505680 @default.
- W3207658114 cites W2170644095 @default.
- W3207658114 cites W2206954826 @default.
- W3207658114 cites W2273723678 @default.
- W3207658114 cites W2342089554 @default.
- W3207658114 cites W2345205020 @default.
- W3207658114 cites W2346866879 @default.
- W3207658114 cites W2359021079 @default.
- W3207658114 cites W2461398495 @default.
- W3207658114 cites W2514294261 @default.