Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice

Abstract Alternative splicing of tau exon 10 generates tau isoforms with three or four microtubule-binding repeats, 3R-tau and 4R-tau, which is equally expressed in adult human brain. Imbalanced expression in 3R-tau and 4R-tau has been found in several sporadic and inherited tauopathies, suggesting...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xiaomin Yin, Nana Jin, Jianhua Shi, Yanchong Zhang, Yue Wu, Cheng-Xin Gong, Khalid Iqbal, Fei Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/55ff45703dc84a5690b2e8a8fb95cd0b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:55ff45703dc84a5690b2e8a8fb95cd0b
record_format	dspace
spelling	oai:doaj.org-article:55ff45703dc84a5690b2e8a8fb95cd0b2021-12-02T16:06:09ZDyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice10.1038/s41598-017-00682-y2045-2322https://doaj.org/article/55ff45703dc84a5690b2e8a8fb95cd0b2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00682-yhttps://doaj.org/toc/2045-2322Abstract Alternative splicing of tau exon 10 generates tau isoforms with three or four microtubule-binding repeats, 3R-tau and 4R-tau, which is equally expressed in adult human brain. Imbalanced expression in 3R-tau and 4R-tau has been found in several sporadic and inherited tauopathies, suggesting that dysregulation of tau exon 10 is sufficient to cause neurodegenerative diseases. We previously reported that Dyrk1A, which is overexpressed in Down syndrome brains, regulates alternative splicing of exogenous tau exon 10. In the present study, we investigated the regulation of endogenous tau exon 10 splicing by Dyrk1A. We found that inhibition of Dyrk1A enhanced tau exon 10 inclusion, leading to an increase in 4R-tau/3R-tau ratio in differentiated-human neuronal progenitors and in the neonatal rat brains. Accompanied with overexpression of Dyrk1A, 3R-tau was increased and 4R-tau was decreased in the neonatal brains of Ts65Dn mice, a model of Down syndrome. Treatment with Dyrk1A inhibitor, green tea flavonol epigallocatechin-gallate (EGCG), from gestation to adulthood suppressed 3R-tau expression and rescued anxiety and memory deficits in Ts65Dn mouse brains. Thus, Dyrk1A might be an ideal therapeutic target for Alzheimer’s disease, especially for Down syndrome and EGCG which inhibits Dyrk1A may have potential effect on the treatment or prevention of this disease.Xiaomin YinNana JinJianhua ShiYanchong ZhangYue WuCheng-Xin GongKhalid IqbalFei LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaomin Yin Nana Jin Jianhua Shi Yanchong Zhang Yue Wu Cheng-Xin Gong Khalid Iqbal Fei Liu Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice
description	Abstract Alternative splicing of tau exon 10 generates tau isoforms with three or four microtubule-binding repeats, 3R-tau and 4R-tau, which is equally expressed in adult human brain. Imbalanced expression in 3R-tau and 4R-tau has been found in several sporadic and inherited tauopathies, suggesting that dysregulation of tau exon 10 is sufficient to cause neurodegenerative diseases. We previously reported that Dyrk1A, which is overexpressed in Down syndrome brains, regulates alternative splicing of exogenous tau exon 10. In the present study, we investigated the regulation of endogenous tau exon 10 splicing by Dyrk1A. We found that inhibition of Dyrk1A enhanced tau exon 10 inclusion, leading to an increase in 4R-tau/3R-tau ratio in differentiated-human neuronal progenitors and in the neonatal rat brains. Accompanied with overexpression of Dyrk1A, 3R-tau was increased and 4R-tau was decreased in the neonatal brains of Ts65Dn mice, a model of Down syndrome. Treatment with Dyrk1A inhibitor, green tea flavonol epigallocatechin-gallate (EGCG), from gestation to adulthood suppressed 3R-tau expression and rescued anxiety and memory deficits in Ts65Dn mouse brains. Thus, Dyrk1A might be an ideal therapeutic target for Alzheimer’s disease, especially for Down syndrome and EGCG which inhibits Dyrk1A may have potential effect on the treatment or prevention of this disease.
format	article
author	Xiaomin Yin Nana Jin Jianhua Shi Yanchong Zhang Yue Wu Cheng-Xin Gong Khalid Iqbal Fei Liu
author_facet	Xiaomin Yin Nana Jin Jianhua Shi Yanchong Zhang Yue Wu Cheng-Xin Gong Khalid Iqbal Fei Liu
author_sort	Xiaomin Yin
title	Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice
title_short	Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice
title_full	Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice
title_fullStr	Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice
title_full_unstemmed	Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice
title_sort	dyrk1a overexpression leads to increase of 3r-tau expression and cognitive deficits in ts65dn down syndrome mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/55ff45703dc84a5690b2e8a8fb95cd0b
work_keys_str_mv	AT xiaominyin dyrk1aoverexpressionleadstoincreaseof3rtauexpressionandcognitivedeficitsints65dndownsyndromemice AT nanajin dyrk1aoverexpressionleadstoincreaseof3rtauexpressionandcognitivedeficitsints65dndownsyndromemice AT jianhuashi dyrk1aoverexpressionleadstoincreaseof3rtauexpressionandcognitivedeficitsints65dndownsyndromemice AT yanchongzhang dyrk1aoverexpressionleadstoincreaseof3rtauexpressionandcognitivedeficitsints65dndownsyndromemice AT yuewu dyrk1aoverexpressionleadstoincreaseof3rtauexpressionandcognitivedeficitsints65dndownsyndromemice AT chengxingong dyrk1aoverexpressionleadstoincreaseof3rtauexpressionandcognitivedeficitsints65dndownsyndromemice AT khalidiqbal dyrk1aoverexpressionleadstoincreaseof3rtauexpressionandcognitivedeficitsints65dndownsyndromemice AT feiliu dyrk1aoverexpressionleadstoincreaseof3rtauexpressionandcognitivedeficitsints65dndownsyndromemice
_version_	1718385089608417280

Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice

Ejemplares similares