Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.

To assess the role of the kynurenine pathway in the pathology of Alzheimer's disease (AD), the expression and localization of key components of the kynurenine pathway including the key regulatory enzyme tryptophan 2,3 dioxygenase (TDO), and the metabolites tryptophan, kynurenine, kynurenic acid...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wei Wu, Joseph A Nicolazzo, Li Wen, Roger Chung, Roger Stankovic, Shisan S Bao, Chai K Lim, Bruce J Brew, Karen M Cullen, Gilles J Guillemin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c69cbd3ce9a345eab273769269126948
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c69cbd3ce9a345eab273769269126948
record_format	dspace
spelling	oai:doaj.org-article:c69cbd3ce9a345eab2737692691269482021-12-02T20:07:25ZExpression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.1932-620310.1371/journal.pone.0059749https://doaj.org/article/c69cbd3ce9a345eab2737692691269482013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23630570/?tool=EBIhttps://doaj.org/toc/1932-6203To assess the role of the kynurenine pathway in the pathology of Alzheimer's disease (AD), the expression and localization of key components of the kynurenine pathway including the key regulatory enzyme tryptophan 2,3 dioxygenase (TDO), and the metabolites tryptophan, kynurenine, kynurenic acid, quinolinic acid and picolinic acid were assessed in different brain regions of triple transgenic AD mice. The expression and cell distribution of TDO and quinolinic acid, and their co-localization with neurofibrillary tangles and senile β amyloid deposition were also determined in hippocampal sections from human AD brains. The expression of TDO mRNA was significantly increased in the cerebellum of AD mouse brain. Immunohistochemistry demonstrated that the density of TDO immuno-positive cells was significantly higher in the AD mice. The production of the excitotoxin quinolinic acid strongly increased in the hippocampus in a progressive and age-dependent manner in AD mice. Significantly higher TDO and indoleamine 2,3 dioxygenase 1 immunoreactivity was observed in the hippocampus of AD patients. Furthermore, TDO co-localizes with quinolinic acid, neurofibrillary tangles-tau and amyloid deposits in the hippocampus of AD. These results show that the kynurenine pathway is over-activated in AD mice. This is the first report demonstrating that TDO is highly expressed in the brains of AD mice and in AD patients, suggesting that TDO-mediated activation of the kynurenine pathway could be involved in neurofibrillary tangles formation and associated with senile plaque. Our study adds to the evidence that the kynurenine pathway may play important roles in the neurodegenerative processes of AD.Wei WuJoseph A NicolazzoLi WenRoger ChungRoger StankovicShisan S BaoChai K LimBruce J BrewKaren M CullenGilles J GuilleminPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e59749 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wei Wu Joseph A Nicolazzo Li Wen Roger Chung Roger Stankovic Shisan S Bao Chai K Lim Bruce J Brew Karen M Cullen Gilles J Guillemin Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.
description	To assess the role of the kynurenine pathway in the pathology of Alzheimer's disease (AD), the expression and localization of key components of the kynurenine pathway including the key regulatory enzyme tryptophan 2,3 dioxygenase (TDO), and the metabolites tryptophan, kynurenine, kynurenic acid, quinolinic acid and picolinic acid were assessed in different brain regions of triple transgenic AD mice. The expression and cell distribution of TDO and quinolinic acid, and their co-localization with neurofibrillary tangles and senile β amyloid deposition were also determined in hippocampal sections from human AD brains. The expression of TDO mRNA was significantly increased in the cerebellum of AD mouse brain. Immunohistochemistry demonstrated that the density of TDO immuno-positive cells was significantly higher in the AD mice. The production of the excitotoxin quinolinic acid strongly increased in the hippocampus in a progressive and age-dependent manner in AD mice. Significantly higher TDO and indoleamine 2,3 dioxygenase 1 immunoreactivity was observed in the hippocampus of AD patients. Furthermore, TDO co-localizes with quinolinic acid, neurofibrillary tangles-tau and amyloid deposits in the hippocampus of AD. These results show that the kynurenine pathway is over-activated in AD mice. This is the first report demonstrating that TDO is highly expressed in the brains of AD mice and in AD patients, suggesting that TDO-mediated activation of the kynurenine pathway could be involved in neurofibrillary tangles formation and associated with senile plaque. Our study adds to the evidence that the kynurenine pathway may play important roles in the neurodegenerative processes of AD.
format	article
author	Wei Wu Joseph A Nicolazzo Li Wen Roger Chung Roger Stankovic Shisan S Bao Chai K Lim Bruce J Brew Karen M Cullen Gilles J Guillemin
author_facet	Wei Wu Joseph A Nicolazzo Li Wen Roger Chung Roger Stankovic Shisan S Bao Chai K Lim Bruce J Brew Karen M Cullen Gilles J Guillemin
author_sort	Wei Wu
title	Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.
title_short	Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.
title_full	Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.
title_fullStr	Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.
title_full_unstemmed	Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.
title_sort	expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human alzheimer's disease brain.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c69cbd3ce9a345eab273769269126948
work_keys_str_mv	AT weiwu expressionoftryptophan23dioxygenaseandproductionofkynureninepathwaymetabolitesintripletransgenicmiceandhumanalzheimersdiseasebrain AT josephanicolazzo expressionoftryptophan23dioxygenaseandproductionofkynureninepathwaymetabolitesintripletransgenicmiceandhumanalzheimersdiseasebrain AT liwen expressionoftryptophan23dioxygenaseandproductionofkynureninepathwaymetabolitesintripletransgenicmiceandhumanalzheimersdiseasebrain AT rogerchung expressionoftryptophan23dioxygenaseandproductionofkynureninepathwaymetabolitesintripletransgenicmiceandhumanalzheimersdiseasebrain AT rogerstankovic expressionoftryptophan23dioxygenaseandproductionofkynureninepathwaymetabolitesintripletransgenicmiceandhumanalzheimersdiseasebrain AT shisansbao expressionoftryptophan23dioxygenaseandproductionofkynureninepathwaymetabolitesintripletransgenicmiceandhumanalzheimersdiseasebrain AT chaiklim expressionoftryptophan23dioxygenaseandproductionofkynureninepathwaymetabolitesintripletransgenicmiceandhumanalzheimersdiseasebrain AT brucejbrew expressionoftryptophan23dioxygenaseandproductionofkynureninepathwaymetabolitesintripletransgenicmiceandhumanalzheimersdiseasebrain AT karenmcullen expressionoftryptophan23dioxygenaseandproductionofkynureninepathwaymetabolitesintripletransgenicmiceandhumanalzheimersdiseasebrain AT gillesjguillemin expressionoftryptophan23dioxygenaseandproductionofkynureninepathwaymetabolitesintripletransgenicmiceandhumanalzheimersdiseasebrain
_version_	1718375327542018048

Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.

Ejemplares similares