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000276822 1001_ $$00000-0001-8801-4711$$aOvesen, Peter Lund$$b0
000276822 245__ $$aAlzheimer's Disease Risk Gene SORL1 Promotes Receptiveness of Human Microglia to Pro-Inflammatory Stimuli.
000276822 260__ $$aBognor Regis [u.a.]$$bWiley-Liss$$c2025
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000276822 520__ $$aSorting protein-related receptor containing class A repeats (SORLA) is an intracellular trafficking receptor encoded by the Alzheimer's disease (AD) gene SORL1 (sortilin-related receptor 1). Recent findings argue that altered expression in microglia may underlie the genome-wide risk of AD seen with some SORL1 gene variants, however, the functional significance of the receptor in microglia remains poorly explained. Using unbiased omics and targeted functional analyses in iPSC-based human microglia, we identified a crucial role for SORLA in sensitizing microglia to pro-inflammatory stimuli. We show that SORLA acts as a sorting factor for the pattern recognition receptor CD14, directing CD14 exposure on the cell surface and priming microglia to stimulation by pro-inflammatory factors. Loss of SORLA in gene-targeted microglia impairs proper CD14 sorting and blunts pro-inflammatory responses. Our studies indicate an important role for SORLA in shaping the inflammatory brain milieu, a biological process important to local immune responses in AD.
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000276822 650_7 $$2Other$$aAlzheimer's disease
000276822 650_7 $$2Other$$aSORLA
000276822 650_7 $$2Other$$aVPS10P domain receptors
000276822 650_7 $$2Other$$abrain inflammation
000276822 650_7 $$2Other$$amicroglia
000276822 650_7 $$2NLM Chemicals$$aSORL1 protein, human
000276822 650_7 $$2NLM Chemicals$$aLDL-Receptor Related Proteins
000276822 650_7 $$2NLM Chemicals$$aMembrane Transport Proteins
000276822 650_7 $$2NLM Chemicals$$aLipopolysaccharide Receptors
000276822 650_7 $$2NLM Chemicals$$aCD14 protein, human
000276822 650_2 $$2MeSH$$aHumans
000276822 650_2 $$2MeSH$$aMicroglia: metabolism
000276822 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000276822 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000276822 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000276822 650_2 $$2MeSH$$aLDL-Receptor Related Proteins: genetics
000276822 650_2 $$2MeSH$$aLDL-Receptor Related Proteins: metabolism
000276822 650_2 $$2MeSH$$aMembrane Transport Proteins: genetics
000276822 650_2 $$2MeSH$$aMembrane Transport Proteins: metabolism
000276822 650_2 $$2MeSH$$aLipopolysaccharide Receptors: metabolism
000276822 650_2 $$2MeSH$$aLipopolysaccharide Receptors: genetics
000276822 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: metabolism
000276822 650_2 $$2MeSH$$aInflammation: metabolism
000276822 650_2 $$2MeSH$$aInflammation: genetics
000276822 7001_ $$aJuul-Madsen, Kristian$$b1
000276822 7001_ $$aTelugu, Narasimha S$$b2
000276822 7001_ $$aSchmidt, Vanessa$$b3
000276822 7001_ $$aFrahm, Silke$$b4
000276822 7001_ $$aRadbruch, Helena$$b5
000276822 7001_ $$aLouth, Emma Louise$$b6
000276822 7001_ $$aKorshøj, Anders Rosendal$$b7
000276822 7001_ $$0P:(DE-2719)2812386$$aHeppner, Frank L$$b8
000276822 7001_ $$aDiecke, Sebastian$$b9
000276822 7001_ $$00000-0001-8208-0291$$aKettenmann, Helmut$$b10
000276822 7001_ $$aWillnow, Thomas E$$b11
000276822 773__ $$0PERI:(DE-600)1474828-9$$a10.1002/glia.24659$$gVol. 73, no. 4, p. 857 - 872$$n4$$p857 - 872$$tGlia$$v73$$x0894-1491$$y2025
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