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- W1978467560 abstract "Amyloid β (Aβ) peptide is hypothesized to stimulate microglia to acquire their characteristic proinflammatory phenotype in Alzheimer’s disease (AD) brains. The specific mechanisms by which Aβ leads to microglial activation remain an area of interest for identifying attractive molecular targets for intervention. Based upon the fact that microglia express the proinflammatory transcription factor, nuclear factor of activated T cells (NFAT), we hypothesized that NFAT activity is required for the Aβ-stimulated microgliosis that occurs during disease. Primary murine microglia cultures were stimulated with Aβ in the absence or presence of NFAT inhibitors, FK506 and tat-VIVIT peptide, to quantify secretion of cytokines, neurotoxins, or Aβ phagocytosis. A transgenic mouse model of AD, APP/PS1, was treated subcutaneously via mini-osmotic pumps with FK506 or tat-VIVIT to quantify effects on cytokines, microgliosis, plaque load, and memory. Expression of various NFAT isoforms was verified in primary murine microglia through Western blot analysis. Microglial cultures were stimulated with Aβ fibrils in the absence or presence of the NFAT inhibitors, FK506 and tat-VIVIT, to demonstrate that NFAT activity regulated Aβ phagocytosis, neurotoxin secretion, and cytokine secretion. Delivery of FK506 and tat-VIVIT to transgenic APP/PS1 mice attenuated spleen but not brain cytokine levels. However, FK506 and tat-VIVIT significantly attenuated both microgliosis and Aβ plaque load in treated mice compared to controls. Surprisingly, this did not correlate with changes in memory performance via T-maze testing. Our findings suggest that development of specific NFAT inhibitors may offer promise as an effective strategy for attenuating the microgliosis and Aβ plaque deposition that occur in AD." @default.
- W1978467560 created "2016-06-24" @default.
- W1978467560 creator A5030274090 @default.
- W1978467560 creator A5043778889 @default.
- W1978467560 creator A5077288236 @default.
- W1978467560 creator A5086869525 @default.
- W1978467560 date "2015-03-04" @default.
- W1978467560 modified "2023-10-18" @default.
- W1978467560 title "Attenuation of microglial activation in a mouse model of Alzheimer’s disease via NFAT inhibition" @default.
- W1978467560 cites W1250647964 @default.
- W1978467560 cites W128004132 @default.
- W1978467560 cites W1545025388 @default.
- W1978467560 cites W1575476617 @default.
- W1978467560 cites W1590954867 @default.
- W1978467560 cites W1772298148 @default.
- W1978467560 cites W1818767073 @default.
- W1978467560 cites W186443576 @default.
- W1978467560 cites W1958041724 @default.
- W1978467560 cites W1964627146 @default.
- W1978467560 cites W1971071413 @default.
- W1978467560 cites W1973238388 @default.
- W1978467560 cites W1974105812 @default.
- W1978467560 cites W1979503919 @default.
- W1978467560 cites W1981513372 @default.
- W1978467560 cites W1982323880 @default.
- W1978467560 cites W1983399609 @default.
- W1978467560 cites W1984754431 @default.
- W1978467560 cites W1984899161 @default.
- W1978467560 cites W1984924722 @default.
- W1978467560 cites W1988278010 @default.
- W1978467560 cites W1990402345 @default.
- W1978467560 cites W1990948040 @default.
- W1978467560 cites W1991210089 @default.
- W1978467560 cites W1991763618 @default.
- W1978467560 cites W1992598058 @default.
- W1978467560 cites W1993124121 @default.
- W1978467560 cites W1993962367 @default.
- W1978467560 cites W1993994868 @default.
- W1978467560 cites W1995961820 @default.
- W1978467560 cites W1999544109 @default.
- W1978467560 cites W2003108859 @default.
- W1978467560 cites W2008481758 @default.
- W1978467560 cites W2011205127 @default.
- W1978467560 cites W2011553901 @default.
- W1978467560 cites W2011989939 @default.
- W1978467560 cites W2012052743 @default.
- W1978467560 cites W2012405907 @default.
- W1978467560 cites W2015068992 @default.
- W1978467560 cites W2019393277 @default.
- W1978467560 cites W2019845863 @default.
- W1978467560 cites W2021322070 @default.
- W1978467560 cites W2023200476 @default.
- W1978467560 cites W2023695563 @default.
- W1978467560 cites W2026181894 @default.
- W1978467560 cites W2028211858 @default.
- W1978467560 cites W2028926219 @default.
- W1978467560 cites W2030452219 @default.
- W1978467560 cites W2032935702 @default.
- W1978467560 cites W2035302673 @default.
- W1978467560 cites W2038611817 @default.
- W1978467560 cites W2040565048 @default.
- W1978467560 cites W2047588114 @default.
- W1978467560 cites W2048085771 @default.
- W1978467560 cites W2056501242 @default.
- W1978467560 cites W2057249855 @default.
- W1978467560 cites W2059195281 @default.
- W1978467560 cites W2060955976 @default.
- W1978467560 cites W2061466239 @default.
- W1978467560 cites W2064243975 @default.
- W1978467560 cites W2065567658 @default.
- W1978467560 cites W2067155622 @default.
- W1978467560 cites W2067244940 @default.
- W1978467560 cites W2069873939 @default.
- W1978467560 cites W2072581984 @default.
- W1978467560 cites W2074954865 @default.
- W1978467560 cites W2076800034 @default.
- W1978467560 cites W2080409041 @default.
- W1978467560 cites W2082331037 @default.
- W1978467560 cites W2083663079 @default.
- W1978467560 cites W2087708847 @default.
- W1978467560 cites W2088590766 @default.
- W1978467560 cites W2089246382 @default.
- W1978467560 cites W2090956512 @default.
- W1978467560 cites W2095372251 @default.
- W1978467560 cites W2106729121 @default.
- W1978467560 cites W2111986089 @default.
- W1978467560 cites W2113690985 @default.
- W1978467560 cites W2115650832 @default.
- W1978467560 cites W2116192463 @default.
- W1978467560 cites W2116931831 @default.
- W1978467560 cites W2128009612 @default.
- W1978467560 cites W2128635872 @default.
- W1978467560 cites W2130476489 @default.
- W1978467560 cites W2140707292 @default.
- W1978467560 cites W2140884549 @default.
- W1978467560 cites W2152901985 @default.
- W1978467560 cites W2153438315 @default.
- W1978467560 cites W2153710780 @default.
- W1978467560 cites W2158676848 @default.
- W1978467560 cites W2159027833 @default.