2021
DOI: 10.1101/2021.01.25.428149
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TREM2is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor

Abstract: Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. We report here that TREM2 is a thyroid hormone regulated gene and its expression in macrophages and microglia is stimu… Show more

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Cited by 3 publications
(2 citation statements)
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References 70 publications
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“…TRβ-selective thyromimetics have been developed [ 100 , 101 , 102 , 103 ] and have been shown to elicit the same transcriptional response as T 3 [ 104 ]. These drugs have been shown to be effective for treatment of metabolic and neurodegenerative disorders in clinical trials and to subvert the negative side-effects of hyperthyroidism [ 105 ], but have not yet been explored as anti-tumor agents.…”
Section: Discussionmentioning
confidence: 99%
“…TRβ-selective thyromimetics have been developed [ 100 , 101 , 102 , 103 ] and have been shown to elicit the same transcriptional response as T 3 [ 104 ]. These drugs have been shown to be effective for treatment of metabolic and neurodegenerative disorders in clinical trials and to subvert the negative side-effects of hyperthyroidism [ 105 ], but have not yet been explored as anti-tumor agents.…”
Section: Discussionmentioning
confidence: 99%
“…Preclinical research indicates that thyroid hormones block APP gene expression by reducing histone H3 acetylation and histone H3 lysine 4 methylation, and thus reduce βA formation ( 79 ). Regulation of TREM2 gene expression on microglia by thyroid hormones has also been demonstrated ( 80 ). If TREM2 dysfunction occurs, it may alter the response of microglia to βA and may be involved in the etiology of Alzheimer’s disease through immune and inflammatory pathways ( 81 ).…”
Section: Thyroid Dysfunction As the Cause Of Admentioning
confidence: 99%