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| 001 | 276473 | ||
| 005 | 20250213091511.0 | ||
| 024 | 7 | _ | |a 10.1016/j.immuni.2025.01.007 |2 doi |
| 024 | 7 | _ | |a 1074-7613 |2 ISSN |
| 024 | 7 | _ | |a 1097-4180 |2 ISSN |
| 024 | 7 | _ | |a altmetric:173782237 |2 altmetric |
| 024 | 7 | _ | |a pmid:39904338 |2 pmid |
| 037 | _ | _ | |a DZNE-2025-00295 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a McManus, Róisín M. |0 P:(DE-2719)2811671 |b 0 |e First author |
| 245 | _ | _ | |a NLRP3-mediated glutaminolysis controls microglial phagocytosis to promote Alzheimer’s disease progression |
| 260 | _ | _ | |a [Cambridge, Mass.] |c 2025 |b Cell Press |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1739434386_23637 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Activation of the NLRP3 inflammasome has been implicated in the pathogenesis of Alzheimer’s disease (AD) via the release of IL-1β and ASC specks. However, whether NLRP3 is involved in pathways beyond this remained unknown. Here, we found that Aβ deposition in vivo directly triggered NLRP3 activation in APP/PS1 mice, which model many features of AD. Loss of NLRP3 increased glutamine- and glutamate-related metabolism and increased expression of microglial Slc1a3, which was associated with enhanced mitochondrial and metabolic activity. The generation of α-ketoglutarate during this process impacted cellular function, including increased clearance of Aβ peptides as well as epigenetic and gene transcription changes. This pathway was conserved between murine and human cells. Critically, we could mimic this effect pharmacologically using NLRP3-specific inhibitors, but only with chronic NLRP3 inhibition. Together, these data demonstrate an additional role for NLRP3, where it can modulate mitochondrial and metabolic function, with important downstream consequences for the progression of AD. |
| 536 | _ | _ | |a 353 - Clinical and Health Care Research (POF4-353) |0 G:(DE-HGF)POF4-353 |c POF4-353 |f POF IV |x 0 |
| 536 | _ | _ | |a 351 - Brain Function (POF4-351) |0 G:(DE-HGF)POF4-351 |c POF4-351 |f POF IV |x 1 |
| 536 | _ | _ | |a 352 - Disease Mechanisms (POF4-352) |0 G:(DE-HGF)POF4-352 |c POF4-352 |f POF IV |x 2 |
| 588 | _ | _ | |a Dataset connected to CrossRef, Journals: pub.dzne.de |
| 650 | _ | 7 | |a Alzheimer’s disease |2 Other |
| 650 | _ | 7 | |a NLRP3 |2 Other |
| 650 | _ | 7 | |a amyloid-β |2 Other |
| 650 | _ | 7 | |a dementia |2 Other |
| 650 | _ | 7 | |a glutamine metabolism |2 Other |
| 650 | _ | 7 | |a inflammasome |2 Other |
| 650 | _ | 7 | |a microglia |2 Other |
| 650 | _ | 7 | |a phagocytosis |2 Other |
| 650 | _ | 7 | |a α-ketoglutarate |2 Other |
| 650 | _ | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM Chemicals |
| 650 | _ | 7 | |a Inflammasomes |2 NLM Chemicals |
| 650 | _ | 7 | |a Glutamine |0 0RH81L854J |2 NLM Chemicals |
| 650 | _ | 7 | |a Amyloid beta-Peptides |2 NLM Chemicals |
| 650 | _ | 7 | |a Nlrp3 protein, mouse |2 NLM Chemicals |
| 650 | _ | 7 | |a Ketoglutaric Acids |2 NLM Chemicals |
| 650 | _ | 2 | |a Alzheimer Disease: metabolism |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a NLR Family, Pyrin Domain-Containing 3 Protein: metabolism |2 MeSH |
| 650 | _ | 2 | |a Microglia: metabolism |2 MeSH |
| 650 | _ | 2 | |a Microglia: immunology |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Disease Progression |2 MeSH |
| 650 | _ | 2 | |a Phagocytosis |2 MeSH |
| 650 | _ | 2 | |a Inflammasomes: metabolism |2 MeSH |
| 650 | _ | 2 | |a Mitochondria: metabolism |2 MeSH |
| 650 | _ | 2 | |a Glutamine: metabolism |2 MeSH |
| 650 | _ | 2 | |a Disease Models, Animal |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Peptides: metabolism |2 MeSH |
| 650 | _ | 2 | |a Mice, Transgenic |2 MeSH |
| 650 | _ | 2 | |a Mice, Knockout |2 MeSH |
| 650 | _ | 2 | |a Ketoglutaric Acids: metabolism |2 MeSH |
| 650 | _ | 2 | |a Mice, Inbred C57BL |2 MeSH |
| 700 | 1 | _ | |a Komes, Max |0 P:(DE-2719)9001384 |b 1 |
| 700 | 1 | _ | |a Griep, Angelika |0 P:(DE-2719)2811029 |b 2 |
| 700 | 1 | _ | |a Santarelli, Francesco |0 P:(DE-2719)2810567 |b 3 |
| 700 | 1 | _ | |a Schwartz, Stephanie |0 P:(DE-HGF)0 |b 4 |
| 700 | 1 | _ | |a Perea, Juan Ramon |0 P:(DE-2719)9002194 |b 5 |
| 700 | 1 | _ | |a Schlachetzki, Johannes C. M. |b 6 |
| 700 | 1 | _ | |a Bouvier, David S. |b 7 |
| 700 | 1 | _ | |a Khalil, Michelle-Amirah |b 8 |
| 700 | 1 | _ | |a Lauterbach, Mario A. |0 P:(DE-HGF)0 |b 9 |
| 700 | 1 | _ | |a Heinemann, Lea |0 P:(DE-HGF)0 |b 10 |
| 700 | 1 | _ | |a Schlüter, Titus |0 P:(DE-HGF)0 |b 11 |
| 700 | 1 | _ | |a Pour, Mehran Shaban |0 P:(DE-HGF)0 |b 12 |
| 700 | 1 | _ | |a Lovotti, Marta |b 13 |
| 700 | 1 | _ | |a Stahl, Rainer |b 14 |
| 700 | 1 | _ | |a Duthie, Fraser |b 15 |
| 700 | 1 | _ | |a Rodríguez-Alcázar, Juan F. |b 16 |
| 700 | 1 | _ | |a Schmidt, Susanne V. |b 17 |
| 700 | 1 | _ | |a Spitzer, Jasper |b 18 |
| 700 | 1 | _ | |a Noori, Peri |b 19 |
| 700 | 1 | _ | |a Maillo, Alberto |b 20 |
| 700 | 1 | _ | |a Boettcher, Andreas |b 21 |
| 700 | 1 | _ | |a Herron, Brian |b 22 |
| 700 | 1 | _ | |a McConville, John |b 23 |
| 700 | 1 | _ | |a Gomez-Cabrero, David |b 24 |
| 700 | 1 | _ | |a Tegnér, Jesper |b 25 |
| 700 | 1 | _ | |a Glass, Christopher K. |b 26 |
| 700 | 1 | _ | |a Hiller, Karsten |b 27 |
| 700 | 1 | _ | |a Latz, Eicke |0 P:(DE-2719)2000062 |b 28 |e Last author |
| 700 | 1 | _ | |a Heneka, Michael |0 P:(DE-2719)2000008 |b 29 |e Last author |
| 773 | _ | _ | |a 10.1016/j.immuni.2025.01.007 |g p. S1074761325000329 |0 PERI:(DE-600)2001966-X |n 2 |p 326 - 343.e11 |t Immunity |v 58 |y 2025 |x 1074-7613 |
| 856 | 4 | _ | |u https://pub.dzne.de/record/276473/files/DZNE-2025-00295_Restricted.pdf |
| 856 | 4 | _ | |u https://pub.dzne.de/record/276473/files/DZNE-2025-00295_Restricted.pdf?subformat=pdfa |x pdfa |
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