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PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal

Impaired neurogenesis has been associated with several brain disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The role of peroxiredoxin 6 (PRDX6) in neurodegenerative diseases is very controversial. To demonstrate the role of PRDX6 in neurogenesis, we compared the neurogenes...

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Autores principales: Yeo, In Jun, Park, Mi Hee, Son, Dong Ju, Kim, Ji Young, Nam, Kyoung Tak, Hyun, Byung Kook, Kim, So Young, Jung, Myung Hee, Song, Min Ji, Chun, Hyung Ok, Lee, Tae Hyung, Han, Sang-Bae, Hong, Jin Tae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476867/
https://www.ncbi.nlm.nih.gov/pubmed/30097850
http://dx.doi.org/10.1007/s12035-018-1287-2
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author Yeo, In Jun
Park, Mi Hee
Son, Dong Ju
Kim, Ji Young
Nam, Kyoung Tak
Hyun, Byung Kook
Kim, So Young
Jung, Myung Hee
Song, Min Ji
Chun, Hyung Ok
Lee, Tae Hyung
Han, Sang-Bae
Hong, Jin Tae
author_facet Yeo, In Jun
Park, Mi Hee
Son, Dong Ju
Kim, Ji Young
Nam, Kyoung Tak
Hyun, Byung Kook
Kim, So Young
Jung, Myung Hee
Song, Min Ji
Chun, Hyung Ok
Lee, Tae Hyung
Han, Sang-Bae
Hong, Jin Tae
author_sort Yeo, In Jun
collection PubMed
description Impaired neurogenesis has been associated with several brain disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The role of peroxiredoxin 6 (PRDX6) in neurodegenerative diseases is very controversial. To demonstrate the role of PRDX6 in neurogenesis, we compared the neurogenesis ability of PRDX6-overexpressing transgenic (Tg) mice and wild-type mice and studied the involved molecular mechanisms. We showed that the neurogenesis of neural stem cells (NSCs) and the expression of the marker protein were lower in PRDX6 Tg-mice than in wild-type mice. To determine the factors involved in PRDX6-related neural stem cell impairment, we performed a microarray experiment. We showed that the expression of WDFY1 was dramatically decreased in PRDX6-Tg mice. Moreover, WDFY1 siRNA decreases the differentiation ability of primary neural stem cells. Interestingly, WDFY1 reportedly recruits the signaling adaptor TIR-domain-containing adapter-inducing interferon-β (TRIF) to toll-like receptors (TLRs); thus, we showed the relationship among TLRs, PRDX6, and WDFY1. We showed that TLR4 was dramatically reduced in PRDX6 Tg mice, and reduced TLR4 expression and neurogenesis was reversed by the introduction of WDFY1 plasmid in the neural stem cells from PRDX6 Tg mice. This study indicated that PRDX6 inhibits the neurogenesis of neural precursor cells through TLR4-dependent downregulation of WDFY1 and suggested that the inhibitory effect of PRDX6 on neurogenesis play a role in the development of neurodegenerative diseases in the PRDX6 overexpressing transgenic mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1287-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-64768672019-05-14 PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal Yeo, In Jun Park, Mi Hee Son, Dong Ju Kim, Ji Young Nam, Kyoung Tak Hyun, Byung Kook Kim, So Young Jung, Myung Hee Song, Min Ji Chun, Hyung Ok Lee, Tae Hyung Han, Sang-Bae Hong, Jin Tae Mol Neurobiol Article Impaired neurogenesis has been associated with several brain disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The role of peroxiredoxin 6 (PRDX6) in neurodegenerative diseases is very controversial. To demonstrate the role of PRDX6 in neurogenesis, we compared the neurogenesis ability of PRDX6-overexpressing transgenic (Tg) mice and wild-type mice and studied the involved molecular mechanisms. We showed that the neurogenesis of neural stem cells (NSCs) and the expression of the marker protein were lower in PRDX6 Tg-mice than in wild-type mice. To determine the factors involved in PRDX6-related neural stem cell impairment, we performed a microarray experiment. We showed that the expression of WDFY1 was dramatically decreased in PRDX6-Tg mice. Moreover, WDFY1 siRNA decreases the differentiation ability of primary neural stem cells. Interestingly, WDFY1 reportedly recruits the signaling adaptor TIR-domain-containing adapter-inducing interferon-β (TRIF) to toll-like receptors (TLRs); thus, we showed the relationship among TLRs, PRDX6, and WDFY1. We showed that TLR4 was dramatically reduced in PRDX6 Tg mice, and reduced TLR4 expression and neurogenesis was reversed by the introduction of WDFY1 plasmid in the neural stem cells from PRDX6 Tg mice. This study indicated that PRDX6 inhibits the neurogenesis of neural precursor cells through TLR4-dependent downregulation of WDFY1 and suggested that the inhibitory effect of PRDX6 on neurogenesis play a role in the development of neurodegenerative diseases in the PRDX6 overexpressing transgenic mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1287-2) contains supplementary material, which is available to authorized users. Springer US 2018-08-10 2019 /pmc/articles/PMC6476867/ /pubmed/30097850 http://dx.doi.org/10.1007/s12035-018-1287-2 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Yeo, In Jun
Park, Mi Hee
Son, Dong Ju
Kim, Ji Young
Nam, Kyoung Tak
Hyun, Byung Kook
Kim, So Young
Jung, Myung Hee
Song, Min Ji
Chun, Hyung Ok
Lee, Tae Hyung
Han, Sang-Bae
Hong, Jin Tae
PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal
title PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal
title_full PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal
title_fullStr PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal
title_full_unstemmed PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal
title_short PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal
title_sort prdx6 inhibits neurogenesis through downregulation of wdfy1-mediated tlr4 signal
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476867/
https://www.ncbi.nlm.nih.gov/pubmed/30097850
http://dx.doi.org/10.1007/s12035-018-1287-2
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