FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3137602493> ?p ?o ?g. }

• W3137602493 abstract "Microglial cells regulate neural homeostasis by coordinating both immune responses and clearance of debris, and the P2X7 receptor for extracellular ATP plays a central role in both functions. The P2X7 receptor is primarily known in microglial cells for its immune signaling and NLRP3 inflammasome activation. However, the receptor also affects the clearance of extracellular and intracellular debris through modifications of lysosomal function, phagocytosis, and autophagy. In the absence of an agonist, the P2X7 receptor acts as a scavenger receptor to phagocytose material. Transient receptor stimulation induces autophagy and increases LC3-II levels, likely through calcium-dependent phosphorylation of AMPK, and activates microglia to an M1 or mixed M1/M2 state. We show an increased expression of Nos2 and Tnfa and a decreased expression of Chil3 (YM1) from primary cultures of brain microglia exposed to high levels of ATP. Sustained stimulation can reduce lysosomal function in microglia by increasing lysosomal pH and slowing autophagosome-lysosome fusion. P2X7 receptor stimulation can also cause lysosomal leakage, and the subsequent rise in cytoplasmic cathepsin B activates the NLRP3 inflammasome leading to caspase-1 cleavage and IL-1β maturation and release. Support for P2X7 receptor activation of the inflammasome following lysosomal leakage comes from data on primary microglia showing IL-1β release following receptor stimulation is inhibited by cathepsin B blocker CA-074. This pathway bridges endolysosomal and inflammatory roles and may provide a key mechanism for the increased inflammation found in age-dependent neurodegenerations characterized by excessive lysosomal accumulations. Regardless of whether the inflammasome is activated via this lysosomal leakage or the better-known K+-efflux pathway, the inflammatory impact of P2X7 receptor stimulation is balanced between the autophagic reduction of inflammasome components and their increase following P2X7-mediated priming. In summary, the P2X7 receptor modulates clearance of extracellular debris by microglial cells and mediates lysosomal damage that can activate the NLRP3 inflammasome. A better understanding of how the P2X7 receptor alters phagocytosis, lysosomal health, inflammation, and autophagy can lead to therapies that balance the inflammatory and clearance roles of microglial cells." @default.
• W3137602493 created "2021-03-29" @default.
• W3137602493 creator A5019814267 @default.
• W3137602493 creator A5062141175 @default.
• W3137602493 date "2021-03-15" @default.
• W3137602493 modified "2023-09-30" @default.
• W3137602493 title "The P2X7 Receptor in Microglial Cells Modulates the Endolysosomal Axis, Autophagy, and Phagocytosis" @default.
• W3137602493 cites W1523693806 @default.
• W3137602493 cites W1548145115 @default.
• W3137602493 cites W1557198343 @default.
• W3137602493 cites W1577501389 @default.
• W3137602493 cites W1593937083 @default.
• W3137602493 cites W1599691548 @default.
• W3137602493 cites W1608504671 @default.
• W3137602493 cites W1621930152 @default.
• W3137602493 cites W175813982 @default.
• W3137602493 cites W1830885889 @default.
• W3137602493 cites W1859128422 @default.
• W3137602493 cites W1959874120 @default.
• W3137602493 cites W1964730685 @default.
• W3137602493 cites W1968017409 @default.
• W3137602493 cites W1970637701 @default.
• W3137602493 cites W1981608729 @default.
• W3137602493 cites W1981893522 @default.
• W3137602493 cites W1991805788 @default.
• W3137602493 cites W1996024251 @default.
• W3137602493 cites W1997982516 @default.
• W3137602493 cites W1999881215 @default.
• W3137602493 cites W2004543572 @default.
• W3137602493 cites W2018626218 @default.
• W3137602493 cites W2028317232 @default.
• W3137602493 cites W2031492796 @default.
• W3137602493 cites W2038370680 @default.
• W3137602493 cites W2042767581 @default.
• W3137602493 cites W2042914937 @default.
• W3137602493 cites W2044649672 @default.
• W3137602493 cites W2048030072 @default.
• W3137602493 cites W2049135473 @default.
• W3137602493 cites W2057822363 @default.
• W3137602493 cites W2058346157 @default.
• W3137602493 cites W2064874359 @default.
• W3137602493 cites W2065551358 @default.
• W3137602493 cites W2066697766 @default.
• W3137602493 cites W2069219003 @default.
• W3137602493 cites W2069893872 @default.
• W3137602493 cites W2072184436 @default.
• W3137602493 cites W2072247427 @default.
• W3137602493 cites W2074306630 @default.
• W3137602493 cites W2076062022 @default.
• W3137602493 cites W2079882002 @default.
• W3137602493 cites W2080718655 @default.
• W3137602493 cites W2082429191 @default.
• W3137602493 cites W2085678065 @default.
• W3137602493 cites W2093705034 @default.
• W3137602493 cites W2094660330 @default.
• W3137602493 cites W2095795382 @default.
• W3137602493 cites W2099588975 @default.
• W3137602493 cites W2101898118 @default.
• W3137602493 cites W2102803338 @default.
• W3137602493 cites W2106105150 @default.
• W3137602493 cites W2108435419 @default.
• W3137602493 cites W2108458879 @default.
• W3137602493 cites W2109070574 @default.
• W3137602493 cites W2111550287 @default.
• W3137602493 cites W2112880160 @default.
• W3137602493 cites W2115825207 @default.
• W3137602493 cites W2119457381 @default.
• W3137602493 cites W2120379009 @default.
• W3137602493 cites W2121610160 @default.
• W3137602493 cites W2124049467 @default.
• W3137602493 cites W2124836944 @default.
• W3137602493 cites W2125843236 @default.
• W3137602493 cites W2127237840 @default.
• W3137602493 cites W2127327360 @default.
• W3137602493 cites W2128548437 @default.
• W3137602493 cites W2128850053 @default.
• W3137602493 cites W2135123296 @default.
• W3137602493 cites W2136123169 @default.
• W3137602493 cites W2136886131 @default.
• W3137602493 cites W2140380746 @default.
• W3137602493 cites W2141530812 @default.
• W3137602493 cites W2142242761 @default.
• W3137602493 cites W2144648226 @default.
• W3137602493 cites W2146495932 @default.
• W3137602493 cites W2147180300 @default.
• W3137602493 cites W2148898943 @default.
• W3137602493 cites W2149777963 @default.
• W3137602493 cites W2150660037 @default.
• W3137602493 cites W2155373881 @default.
• W3137602493 cites W2157551652 @default.
• W3137602493 cites W2170959966 @default.
• W3137602493 cites W2255941445 @default.
• W3137602493 cites W2257422503 @default.
• W3137602493 cites W2280077905 @default.
• W3137602493 cites W2291170236 @default.
• W3137602493 cites W2346760531 @default.
• W3137602493 cites W2419021136 @default.
• W3137602493 cites W2439312023 @default.
• W3137602493 cites W2465699308 @default.
• W3137602493 cites W2504803702 @default.

• next