In:
Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-4-6)
Abstract:
Amyloid β (Aβ) and/or ATP activate the NLRP3 inflammasome (N3I) via P2X7R in microglia, which is crucial in neuroinflammation in Alzheimer’s disease (AD). Due to polymorphisms, subtypes, and ubiquitous expression of P2X7R, inhibition of P2X7R has not been effective for AD. We first report that taurodeoxycholate (TDCA), a GPCR19 ligand, inhibited the priming phase of N3I activation, suppressed P2X7R expression and P2X7R-mediated Ca ++ mobilization and N3I oligomerization, which is essential for production of IL-1β/IL-18 by microglia. Furthermore, TDCA enhanced phagocytosis of Aβ and decreased the number of Aβ plaques in the brains of 5x Familial Alzheimer’s disease (5xFAD) mice. TDCA also reduced microgliosis, prevented neuronal loss, and improved memory function in 5xFAD mice. The pleiotropic roles of GPCR19 in P2X7R-mediated N3I activation suggest that targeting GPCR19 might resolve neuroinflammation in AD patients.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2022.766919
DOI:
10.3389/fimmu.2022.766919.s001
DOI:
10.3389/fimmu.2022.766919.s002
DOI:
10.3389/fimmu.2022.766919.s003
DOI:
10.3389/fimmu.2022.766919.s004
DOI:
10.3389/fimmu.2022.766919.s005
DOI:
10.3389/fimmu.2022.766919.s006
DOI:
10.3389/fimmu.2022.766919.s007
DOI:
10.3389/fimmu.2022.766919.s008
DOI:
10.3389/fimmu.2022.766919.s009
DOI:
10.3389/fimmu.2022.766919.s010
DOI:
10.3389/fimmu.2022.766919.s011
DOI:
10.3389/fimmu.2022.766919.s012
DOI:
10.3389/fimmu.2022.766919.s013
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8
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