Home > Publications Database > Alzheimer's Disease Risk Gene SORL1 Promotes Receptiveness of Human Microglia to Pro-Inflammatory Stimuli. > print

001     276822
005     20250323000854.0
024 7 _ |a 10.1002/glia.24659
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024 7 _ |a 1098-1136
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037 _ _ |a DZNE-2025-00335
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Ovesen, Peter Lund
|0 0000-0001-8801-4711
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245 _ _ |a Alzheimer's Disease Risk Gene SORL1 Promotes Receptiveness of Human Microglia to Pro-Inflammatory Stimuli.
260 _ _ |a Bognor Regis [u.a.]
|c 2025
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520 _ _ |a Sorting 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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650 _ 7 |a Alzheimer's disease
|2 Other
650 _ 7 |a SORLA
|2 Other
650 _ 7 |a VPS10P domain receptors
|2 Other
650 _ 7 |a brain inflammation
|2 Other
650 _ 7 |a microglia
|2 Other
650 _ 7 |a SORL1 protein, human
|2 NLM Chemicals
650 _ 7 |a LDL-Receptor Related Proteins
|2 NLM Chemicals
650 _ 7 |a Membrane Transport Proteins
|2 NLM Chemicals
650 _ 7 |a Lipopolysaccharide Receptors
|2 NLM Chemicals
650 _ 7 |a CD14 protein, human
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a LDL-Receptor Related Proteins: genetics
|2 MeSH
650 _ 2 |a LDL-Receptor Related Proteins: metabolism
|2 MeSH
650 _ 2 |a Membrane Transport Proteins: genetics
|2 MeSH
650 _ 2 |a Membrane Transport Proteins: metabolism
|2 MeSH
650 _ 2 |a Lipopolysaccharide Receptors: metabolism
|2 MeSH
650 _ 2 |a Lipopolysaccharide Receptors: genetics
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Inflammation: metabolism
|2 MeSH
650 _ 2 |a Inflammation: genetics
|2 MeSH
700 1 _ |a Juul-Madsen, Kristian
|b 1
700 1 _ |a Telugu, Narasimha S
|b 2
700 1 _ |a Schmidt, Vanessa
|b 3
700 1 _ |a Frahm, Silke
|b 4
700 1 _ |a Radbruch, Helena
|b 5
700 1 _ |a Louth, Emma Louise
|b 6
700 1 _ |a Korshøj, Anders Rosendal
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700 1 _ |a Heppner, Frank L
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700 1 _ |a Diecke, Sebastian
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700 1 _ |a Kettenmann, Helmut
|0 0000-0001-8208-0291
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700 1 _ |a Willnow, Thomas E
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773 _ _ |a 10.1002/glia.24659
|g Vol. 73, no. 4, p. 857 - 872
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