{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Toral-Rios D"],"funding":["Alzheimer’s Association","NCATS NIH HHS","NIA NIH HHS","NIDDK NIH HHS","National Institutes of Health","Hope Center for Neurological Disorders","Alzheimer's Association","National Institute on Aging","NIH HHS","Institute of Clinical and Translational Sciences"],"pagination":["e20232000"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10908359"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["221(4)"],"pubmed_abstract":["Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles, in addition to neuroinflammation and changes in brain lipid metabolism. 25-Hydroxycholesterol (25-HC), a known modulator of both inflammation and lipid metabolism, is produced by cholesterol 25-hydroxylase encoded by Ch25h expressed as a \"disease-associated microglia\" signature gene. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25-HC, there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene. Transcriptomic analyses of bulk hippocampal tissue and single nuclei revealed that Ch25h deficiency in PS19 mice strongly suppressed proinflammatory signaling in microglia. Our results suggest a key role for Ch25h/25-HC in potentiating proinflammatory signaling to promote tau-mediated neurodegeneration. Ch25h may represent a novel therapeutic target for primary tauopathies, AD, and other neuroinflammatory diseases."],"journal":["The Journal of experimental medicine"],"pubmed_title":["Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy."],"pmcid":["PMC10908359"],"funding_grant_id":["R01 AG061729","P30 AG013319","U19 AG069701","AACSF-18-564776","UL1 TR002345","R01 AG081419","5P30AG019610","P30 AG072980","P30 DK056341","#UL1TR002345","U19AG069701","P30 AG019610","R01AG081419","K08 AG068611","K08AG068611"],"pubmed_authors":["Strickland MR","Cashikar AG","Long JM","Paul SM","Han X","Holtzman DM","Ulrich JD","Toral-Rios D","Yu J"],"additional_accession":[]},"is_claimable":false,"name":"Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy.","description":"Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles, in addition to neuroinflammation and changes in brain lipid metabolism. 25-Hydroxycholesterol (25-HC), a known modulator of both inflammation and lipid metabolism, is produced by cholesterol 25-hydroxylase encoded by Ch25h expressed as a \"disease-associated microglia\" signature gene. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25-HC, there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene. Transcriptomic analyses of bulk hippocampal tissue and single nuclei revealed that Ch25h deficiency in PS19 mice strongly suppressed proinflammatory signaling in microglia. Our results suggest a key role for Ch25h/25-HC in potentiating proinflammatory signaling to promote tau-mediated neurodegeneration. Ch25h may represent a novel therapeutic target for primary tauopathies, AD, and other neuroinflammatory diseases.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-04-08T01:21:24.249Z","creation":"2025-04-06T16:47:17.006Z"},"accession":"S-EPMC10908359","cross_references":{"pubmed":["38442267"],"doi":["10.1084/jem.20232000"]}}