Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer’s disease

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to dementia and behavioral changes. Extracellular deposition of amyloid plaques (Aβ) and intracellular deposition of neurofibrillary tangles in neurons are the major pathogenicities of AD. However, drugs ta...

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Autores principales:	Renuka Prasad, Hwajin Jung, Anderson Tan, Yonghee Song, Sungho Moon, Mohammed R. Shaker, Woong Sun, Junghee Lee, Hoon Ryu, Hyun Kook Lim, Eek-hoon Jho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2059ccfe55644e8bae90c637012f62df
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spelling	oai:doaj.org-article:2059ccfe55644e8bae90c637012f62df2021-12-02T17:13:17ZHypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer’s disease10.1038/s41598-021-99562-92045-2322https://doaj.org/article/2059ccfe55644e8bae90c637012f62df2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99562-9https://doaj.org/toc/2045-2322Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to dementia and behavioral changes. Extracellular deposition of amyloid plaques (Aβ) and intracellular deposition of neurofibrillary tangles in neurons are the major pathogenicities of AD. However, drugs targeting these therapeutic targets are not effective. Therefore, novel targets for the treatment of AD urgently need to be identified. Expression of the mesoderm-specific transcript (Mest) is regulated by genomic imprinting, where only the paternal allele is active for transcription. We identified hypermethylation on the Mest promoter, which led to a reduction in Mest mRNA levels and activation of Wnt signaling in brain tissues of AD patients. Mest knockout (KO) using the CRIPSR/Cas9 system in mouse embryonic stem cells and P19 embryonic carcinoma cells leads to neuronal differentiation arrest. Depletion of Mest in primary hippocampal neurons via lentivirus expressing shMest or inducible KO system causes neurodegeneration. Notably, depletion of Mest in primary cortical neurons of rats leads to tau phosphorylation at the S199 and T231 sites. Overall, our data suggest that hypermethylation of the Mest promoter may cause or facilitate the progression of AD.Renuka PrasadHwajin JungAnderson TanYonghee SongSungho MoonMohammed R. ShakerWoong SunJunghee LeeHoon RyuHyun Kook LimEek-hoon JhoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Renuka Prasad Hwajin Jung Anderson Tan Yonghee Song Sungho Moon Mohammed R. Shaker Woong Sun Junghee Lee Hoon Ryu Hyun Kook Lim Eek-hoon Jho Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer’s disease
description	Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to dementia and behavioral changes. Extracellular deposition of amyloid plaques (Aβ) and intracellular deposition of neurofibrillary tangles in neurons are the major pathogenicities of AD. However, drugs targeting these therapeutic targets are not effective. Therefore, novel targets for the treatment of AD urgently need to be identified. Expression of the mesoderm-specific transcript (Mest) is regulated by genomic imprinting, where only the paternal allele is active for transcription. We identified hypermethylation on the Mest promoter, which led to a reduction in Mest mRNA levels and activation of Wnt signaling in brain tissues of AD patients. Mest knockout (KO) using the CRIPSR/Cas9 system in mouse embryonic stem cells and P19 embryonic carcinoma cells leads to neuronal differentiation arrest. Depletion of Mest in primary hippocampal neurons via lentivirus expressing shMest or inducible KO system causes neurodegeneration. Notably, depletion of Mest in primary cortical neurons of rats leads to tau phosphorylation at the S199 and T231 sites. Overall, our data suggest that hypermethylation of the Mest promoter may cause or facilitate the progression of AD.
format	article
author	Renuka Prasad Hwajin Jung Anderson Tan Yonghee Song Sungho Moon Mohammed R. Shaker Woong Sun Junghee Lee Hoon Ryu Hyun Kook Lim Eek-hoon Jho
author_facet	Renuka Prasad Hwajin Jung Anderson Tan Yonghee Song Sungho Moon Mohammed R. Shaker Woong Sun Junghee Lee Hoon Ryu Hyun Kook Lim Eek-hoon Jho
author_sort	Renuka Prasad
title	Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer’s disease
title_short	Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer’s disease
title_full	Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer’s disease
title_fullStr	Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer’s disease
title_full_unstemmed	Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer’s disease
title_sort	hypermethylation of mest promoter causes aberrant wnt signaling in patients with alzheimer’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2059ccfe55644e8bae90c637012f62df
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Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer’s disease

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