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• W4386095660 abstract "Abstract Alzheimer’s disease (AD) is the leading cause of dementia in older adults, and the need for effective, sustainable therapeutic targets is imperative. Pharmacologic inhibition of C5aR1 reduces plaque load, gliosis and memory deficits in animal models. However, the cellular basis underlying this neuroprotection and which processes were the consequence of amyloid reduction vs alteration of the response to amyloid were unclear. In the Arctic model, the C5aR1 antagonist PMX205 did not reduce plaque load, but deficits in short-term memory in female mice were prevented. Hippocampal single cell and single nucleus RNA-seq clusters revealed C5aR1 dependent and independent gene expression and cell-cell communication. Microglial clusters containing neurotoxic disease-associated microglial genes were robustly upregulated in Arctic mice and drastically reduced with PMX205 treatment, while genes in microglia clusters that were overrepresented in the Arctic-PMX205 vs Arctic group were associated with synapse organization and transmission and learning. PMX205 treatment also reduced some A-1 astrocyte genes. In spite of changes in transcript levels, overall protein levels of some reactive glial markers were relatively unchanged by C5aR1 antagonism, as were clusters associated with protective responses to injury. C5aR1 inhibition promoted signaling pathways associated with cell growth and repair, such as TGFβ and FGF, in Arctic mice, while suppressing inflammatory pathways including PROS, Pecam1, and EPHA. In conclusion, pharmacologic C5aR1 inhibition prevents cognitive loss, limits microglial polarization to a detrimental inflammatory state and permits neuroprotective responses, as well as leaving protective functions of complement intact, making C5aR1 antagonism an attractive therapeutic strategy for individuals with AD. One Sentence Summary Pharmacologic inhibition of C5aR1 suppresses disease-enhancing processes and promotes disease mitigating pathways in an aggressive model of Alzheimer’s disease." @default.
• W4386095660 created "2023-08-24" @default.
• W4386095660 creator A5006946812 @default.
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• W4386095660 creator A5092680229 @default.
• W4386095660 date "2023-08-22" @default.
• W4386095660 modified "2023-09-26" @default.
• W4386095660 title "C5aR1 antagonism suppresses inflammatory glial gene expression and alters cellular signaling in an aggressive Alzheimer's model" @default.
• W4386095660 cites W121388512 @default.
• W4386095660 cites W1644276928 @default.
• W4386095660 cites W1748516712 @default.
• W4386095660 cites W1771958278 @default.
• W4386095660 cites W1967301075 @default.
• W4386095660 cites W1968240259 @default.
• W4386095660 cites W1979958331 @default.
• W4386095660 cites W1980565738 @default.
• W4386095660 cites W1989626232 @default.
• W4386095660 cites W1993136341 @default.
• W4386095660 cites W1998723427 @default.
• W4386095660 cites W2001535531 @default.
• W4386095660 cites W2008386957 @default.
• W4386095660 cites W2030164772 @default.
• W4386095660 cites W2035355245 @default.
• W4386095660 cites W2057035225 @default.
• W4386095660 cites W2083758179 @default.
• W4386095660 cites W2087375743 @default.
• W4386095660 cites W2087607255 @default.
• W4386095660 cites W2089718732 @default.
• W4386095660 cites W2092314927 @default.
• W4386095660 cites W2096327192 @default.
• W4386095660 cites W2100902668 @default.
• W4386095660 cites W2114982184 @default.
• W4386095660 cites W2119211366 @default.
• W4386095660 cites W2122743846 @default.
• W4386095660 cites W2124836944 @default.
• W4386095660 cites W2138284015 @default.
• W4386095660 cites W2152729283 @default.
• W4386095660 cites W2155172987 @default.
• W4386095660 cites W2155894885 @default.
• W4386095660 cites W2156164343 @default.
• W4386095660 cites W2164511273 @default.
• W4386095660 cites W2265799967 @default.
• W4386095660 cites W2504925882 @default.
• W4386095660 cites W2508051727 @default.
• W4386095660 cites W2556782482 @default.
• W4386095660 cites W2571948850 @default.
• W4386095660 cites W2572710398 @default.
• W4386095660 cites W2579878933 @default.
• W4386095660 cites W2580909157 @default.
• W4386095660 cites W2586509994 @default.
• W4386095660 cites W2594676718 @default.
• W4386095660 cites W2622807556 @default.
• W4386095660 cites W2755269870 @default.
• W4386095660 cites W2769984699 @default.
• W4386095660 cites W2802319672 @default.
• W4386095660 cites W2806131738 @default.
• W4386095660 cites W2892281512 @default.
• W4386095660 cites W2892345931 @default.
• W4386095660 cites W2950127851 @default.
• W4386095660 cites W2965717703 @default.
• W4386095660 cites W2969235541 @default.
• W4386095660 cites W2969396388 @default.
• W4386095660 cites W2975507539 @default.
• W4386095660 cites W2986782615 @default.
• W4386095660 cites W2998859017 @default.
• W4386095660 cites W3004279507 @default.
• W4386095660 cites W3004547734 @default.
• W4386095660 cites W3019520705 @default.
• W4386095660 cites W3040942181 @default.
• W4386095660 cites W3043633851 @default.
• W4386095660 cites W3095420140 @default.
• W4386095660 cites W3109073748 @default.
• W4386095660 cites W3118773559 @default.
• W4386095660 cites W3121132624 @default.
• W4386095660 cites W3126671350 @default.
• W4386095660 cites W3132661792 @default.
• W4386095660 cites W3154885935 @default.
• W4386095660 cites W3164692211 @default.
• W4386095660 cites W3180278111 @default.
• W4386095660 cites W3196441931 @default.
• W4386095660 cites W3202223582 @default.
• W4386095660 cites W3217724729 @default.
• W4386095660 cites W4200206480 @default.
• W4386095660 cites W4220661922 @default.
• W4386095660 cites W4220825176 @default.
• W4386095660 cites W4224055741 @default.
• W4386095660 cites W4224694754 @default.
• W4386095660 cites W4225133903 @default.
• W4386095660 cites W4225491855 @default.
• W4386095660 cites W4285095021 @default.
• W4386095660 cites W4292092957 @default.
• W4386095660 cites W4312179313 @default.
• W4386095660 cites W4318925869 @default.
• W4386095660 cites W4327675683 @default.

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