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- W3109675223 abstract "Longitudinal preclinical and clinical studies suggest that Aβ drives neurite and synapse degeneration through an array of tau-dependent and independent mechanisms. The intracellular signaling networks regulated by the p75 neurotrophin receptor (p75NTR) substantially overlap with those linked to Aβ and to tau. Here we examine the hypothesis that modulation of p75NTR will suppress the generation of multiple potentially pathogenic tau species and related signaling to protect dendritic spines and processes from Aβ-induced injury. In neurons exposed to oligomeric Aβ in vitro and APP mutant mouse models, modulation of p75NTR signaling using the small-molecule LM11A-31 was found to inhibit Aβ-associated degeneration of neurites and spines; and tau phosphorylation, cleavage, oligomerization and missorting. In line with these effects on tau, LM11A-31 inhibited excess activation of Fyn kinase and its targets, tau and NMDA-NR2B, and decreased Rho kinase signaling changes and downstream aberrant cofilin phosphorylation. In vitro studies with pseudohyperphosphorylated tau and constitutively active RhoA revealed that LM11A-31 likely acts principally upstream of tau phosphorylation, and has effects preventing spine loss both up and downstream of RhoA activation. These findings support the hypothesis that modulation of p75NTR signaling inhibits a broad spectrum of Aβ-triggered, tau-related molecular pathology thereby contributing to synaptic resilience." @default.
- W3109675223 created "2020-12-07" @default.
- W3109675223 creator A5008974845 @default.
- W3109675223 creator A5019824956 @default.
- W3109675223 creator A5030996349 @default.
- W3109675223 creator A5077249061 @default.
- W3109675223 creator A5079616106 @default.
- W3109675223 date "2020-11-23" @default.
- W3109675223 modified "2023-10-15" @default.
- W3109675223 title "Small molecule modulation of the p75 neurotrophin receptor inhibits multiple amyloid beta-induced tau pathologies" @default.
- W3109675223 cites W1425714453 @default.
- W3109675223 cites W1487796157 @default.
- W3109675223 cites W1524723619 @default.
- W3109675223 cites W1536163662 @default.
- W3109675223 cites W1541377218 @default.
- W3109675223 cites W1586525305 @default.
- W3109675223 cites W1598852457 @default.
- W3109675223 cites W1615902322 @default.
- W3109675223 cites W1854589240 @default.
- W3109675223 cites W1893185987 @default.
- W3109675223 cites W1963965739 @default.
- W3109675223 cites W1965049154 @default.
- W3109675223 cites W1965670425 @default.
- W3109675223 cites W1968553823 @default.
- W3109675223 cites W1968937229 @default.
- W3109675223 cites W1972886222 @default.
- W3109675223 cites W1976118830 @default.
- W3109675223 cites W1979022435 @default.
- W3109675223 cites W1982487434 @default.
- W3109675223 cites W1984924722 @default.
- W3109675223 cites W1988224167 @default.
- W3109675223 cites W1988332799 @default.
- W3109675223 cites W1989856924 @default.
- W3109675223 cites W1990423035 @default.
- W3109675223 cites W1993465897 @default.
- W3109675223 cites W1999591105 @default.
- W3109675223 cites W2000655392 @default.
- W3109675223 cites W2002181764 @default.
- W3109675223 cites W2004982110 @default.
- W3109675223 cites W2006083013 @default.
- W3109675223 cites W2016676864 @default.
- W3109675223 cites W2017899473 @default.
- W3109675223 cites W2019012834 @default.
- W3109675223 cites W2022532556 @default.
- W3109675223 cites W2024041849 @default.
- W3109675223 cites W2024989540 @default.
- W3109675223 cites W2027619670 @default.
- W3109675223 cites W2028329342 @default.
- W3109675223 cites W2029960796 @default.
- W3109675223 cites W2030769095 @default.
- W3109675223 cites W2031346817 @default.
- W3109675223 cites W2041512773 @default.
- W3109675223 cites W2041956586 @default.
- W3109675223 cites W2055453151 @default.
- W3109675223 cites W2055583081 @default.
- W3109675223 cites W2056313099 @default.
- W3109675223 cites W2056400639 @default.
- W3109675223 cites W2057007228 @default.
- W3109675223 cites W2061619331 @default.
- W3109675223 cites W2062772621 @default.
- W3109675223 cites W2062839463 @default.
- W3109675223 cites W2064470441 @default.
- W3109675223 cites W2064587868 @default.
- W3109675223 cites W2064971374 @default.
- W3109675223 cites W2074059686 @default.
- W3109675223 cites W2078127569 @default.
- W3109675223 cites W2080899976 @default.
- W3109675223 cites W2081768441 @default.
- W3109675223 cites W2081868034 @default.
- W3109675223 cites W2081903103 @default.
- W3109675223 cites W2082429191 @default.
- W3109675223 cites W2085323811 @default.
- W3109675223 cites W2090434536 @default.
- W3109675223 cites W2092348167 @default.
- W3109675223 cites W2092607846 @default.
- W3109675223 cites W2093279875 @default.
- W3109675223 cites W2095075524 @default.
- W3109675223 cites W2098759196 @default.
- W3109675223 cites W2100722409 @default.
- W3109675223 cites W2101257013 @default.
- W3109675223 cites W2101715910 @default.
- W3109675223 cites W2102795669 @default.
- W3109675223 cites W2125172225 @default.
- W3109675223 cites W2125985978 @default.
- W3109675223 cites W2127604118 @default.
- W3109675223 cites W2130473558 @default.
- W3109675223 cites W2134565622 @default.
- W3109675223 cites W2140323904 @default.
- W3109675223 cites W2140572389 @default.
- W3109675223 cites W2140668393 @default.
- W3109675223 cites W2142118427 @default.
- W3109675223 cites W2142483960 @default.
- W3109675223 cites W2142867910 @default.
- W3109675223 cites W2151252981 @default.
- W3109675223 cites W2152889673 @default.
- W3109675223 cites W2155049938 @default.
- W3109675223 cites W2157317643 @default.
- W3109675223 cites W2162847877 @default.
- W3109675223 cites W2169482634 @default.
- W3109675223 cites W2221779674 @default.