Thyroid hormone regulation of APP (b-amyloid precursor protein) gene expression in brain and brain cultured cells

We have previously shown that the thyroid hormone triiodothyronine negatively regulates the transcrip tional activity of the b-amyloid precursor protein gene (APP) in cultured murine neuroblastoma cells, by a mechanism that involves binding of the nuclear thyroid hormone receptor (TR) to DNA sequenc...

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Bibliographic Details
Authors: Contreras Jurado, Silvia Constanza, Pascual, Angel
Format: article
Publication Date:2012
Country:España
Institution:Universidad Alfonso X el Sabio
Repository:Repositorio Institucional de la Universidad Alfonso X el Sabio
Language:English
OAI Identifier:oai:archive.uax.com:20.500.12080/26179
Online Access:https://hdl.handle.net/20.500.12080/26179
Access Level:Open access
Keyword:Amyloid precursor protein ,Thyroid hormone, Hypothyroidism ,TR knockout, Brain
Description
Summary:We have previously shown that the thyroid hormone triiodothyronine negatively regulates the transcrip tional activity of the b-amyloid precursor protein gene (APP) in cultured murine neuroblastoma cells, by a mechanism that involves binding of the nuclear thyroid hormone receptor (TR) to DNA sequences located within the first exon of the gene. In this report we present results showing that the thyroid hormones also repress the expression of APP in human neuroblastoma cells and in primary cultures of rat neurons. In addition, and in agreement with the results obtained in cultured cells, APP messenger RNA and protein levels are significantly higher in the brain of hypothyroid rats and mice, and also in Alzheimer-related brain regions dissected from KO mice lacking TRs. These results show that binding of the thyroid hor mones to their nuclear receptors mediate their repressive effect on APP gene expression in vivo

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