The lysosome system is severely impaired in a cellular model of neurodegeneration induced by HSV-1 and oxidative stress

The causal agent(s) and molecular mechanisms of Alzheimer's disease (AD) remain unclear. Mounting evidence suggests that herpes simplex virus type 1 (HSV-1) infection is involved in the AD pathogenesis. Oxidative stress (OS) may also be crucial in the AD development. Our group previously report...

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Authors: Kristen, Henrike, Sastre, Isabel, Muñoz-Galdeano, Teresa, Recuero, María, Aludo, Jesús, Bullido Gómez-Heras, María Jesús
Format: article
Publication Date:2018
Country:España
Institution:Universidad Autónoma de Madrid
Repository:Biblos-e Archivo. Repositorio Institucional de la UAM
Language:English
OAI Identifier:oai:repositorio.uam.es:10486/684627
Online Access:http://hdl.handle.net/10486/684627
https://dx.doi.org/10.1016/j.neurobiolaging.2018.03.025
Access Level:Open access
Keyword:HSV-1 infection
Lysosome
Neurodegeneration
Microarrays
Alzheimer´s disease
Biología y Biomedicina / Biología
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spelling The lysosome system is severely impaired in a cellular model of neurodegeneration induced by HSV-1 and oxidative stressKristen, HenrikeSastre, IsabelMuñoz-Galdeano, TeresaRecuero, MaríaAludo, JesúsBullido Gómez-Heras, María JesúsHSV-1 infectionLysosomeNeurodegenerationMicroarraysAlzheimer´s diseaseBiología y Biomedicina / BiologíaThe causal agent(s) and molecular mechanisms of Alzheimer's disease (AD) remain unclear. Mounting evidence suggests that herpes simplex virus type 1 (HSV-1) infection is involved in the AD pathogenesis. Oxidative stress (OS) may also be crucial in the AD development. Our group previously reported that both HSV-1 and OS trigger the appearance of AD-type neurodegeneration markers. The main aim of the present study was to identify the mechanisms involved in this triggering. Expression studies revealed the involvement of a set of OS-regulated genes in HSV-1-infected cells and in cells harboring the Swedish mutation of the amyloid beta precursor protein gene. Functional annotation of these genes revealed the lysosome system to be impaired, suggesting that the interaction of OS with both HSV-1 and amyloid beta precursor protein mutations affects lysosomal function. Functional studies revealed HSV-1 infection and OS to increase the lysosome load, reduce the activity of lysosomal hydrolases, affect cathepsin maturation, and inhibit the endocytosis-mediated degradation of the epidermal growth factor receptor. These findings suggest alterations in the lysosome system to be involved in different forms of ADHeniike Kristen is recipient of a UAM-CSIC International Excellence Campus research contract.Institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO are also acknowledged. This work was supported by the Spanish Ministerio de Ciencia e Innovación (SAF2014-53954-R)Elsevier Inc.Departamento de Biología MolecularFacultad de CienciasCentro de Biología Molecular Severo Ochoa (CBM)Instituto de Investigación Sanitaria del Hospital Universitario de La Paz (IdiPAZ)20182018-03-29research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/684627https://dx.doi.org/10.1016/j.neurobiolaging.2018.03.025reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6846272026-06-23T12:46:27Z
dc.title.none.fl_str_mv The lysosome system is severely impaired in a cellular model of neurodegeneration induced by HSV-1 and oxidative stress
title The lysosome system is severely impaired in a cellular model of neurodegeneration induced by HSV-1 and oxidative stress
spellingShingle The lysosome system is severely impaired in a cellular model of neurodegeneration induced by HSV-1 and oxidative stress
Kristen, Henrike
HSV-1 infection
Lysosome
Neurodegeneration
Microarrays
Alzheimer´s disease
Biología y Biomedicina / Biología
title_short The lysosome system is severely impaired in a cellular model of neurodegeneration induced by HSV-1 and oxidative stress
title_full The lysosome system is severely impaired in a cellular model of neurodegeneration induced by HSV-1 and oxidative stress
title_fullStr The lysosome system is severely impaired in a cellular model of neurodegeneration induced by HSV-1 and oxidative stress
title_full_unstemmed The lysosome system is severely impaired in a cellular model of neurodegeneration induced by HSV-1 and oxidative stress
title_sort The lysosome system is severely impaired in a cellular model of neurodegeneration induced by HSV-1 and oxidative stress
dc.creator.none.fl_str_mv Kristen, Henrike
Sastre, Isabel
Muñoz-Galdeano, Teresa
Recuero, María
Aludo, Jesús
Bullido Gómez-Heras, María Jesús
author Kristen, Henrike
author_facet Kristen, Henrike
Sastre, Isabel
Muñoz-Galdeano, Teresa
Recuero, María
Aludo, Jesús
Bullido Gómez-Heras, María Jesús
author_role author
author2 Sastre, Isabel
Muñoz-Galdeano, Teresa
Recuero, María
Aludo, Jesús
Bullido Gómez-Heras, María Jesús
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
Centro de Biología Molecular Severo Ochoa (CBM)
Instituto de Investigación Sanitaria del Hospital Universitario de La Paz (IdiPAZ)
dc.subject.none.fl_str_mv HSV-1 infection
Lysosome
Neurodegeneration
Microarrays
Alzheimer´s disease
Biología y Biomedicina / Biología
topic HSV-1 infection
Lysosome
Neurodegeneration
Microarrays
Alzheimer´s disease
Biología y Biomedicina / Biología
description The causal agent(s) and molecular mechanisms of Alzheimer's disease (AD) remain unclear. Mounting evidence suggests that herpes simplex virus type 1 (HSV-1) infection is involved in the AD pathogenesis. Oxidative stress (OS) may also be crucial in the AD development. Our group previously reported that both HSV-1 and OS trigger the appearance of AD-type neurodegeneration markers. The main aim of the present study was to identify the mechanisms involved in this triggering. Expression studies revealed the involvement of a set of OS-regulated genes in HSV-1-infected cells and in cells harboring the Swedish mutation of the amyloid beta precursor protein gene. Functional annotation of these genes revealed the lysosome system to be impaired, suggesting that the interaction of OS with both HSV-1 and amyloid beta precursor protein mutations affects lysosomal function. Functional studies revealed HSV-1 infection and OS to increase the lysosome load, reduce the activity of lysosomal hydrolases, affect cathepsin maturation, and inhibit the endocytosis-mediated degradation of the epidermal growth factor receptor. These findings suggest alterations in the lysosome system to be involved in different forms of AD
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-03-29
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/684627
https://dx.doi.org/10.1016/j.neurobiolaging.2018.03.025
url http://hdl.handle.net/10486/684627
https://dx.doi.org/10.1016/j.neurobiolaging.2018.03.025
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier Inc.
publisher.none.fl_str_mv Elsevier Inc.
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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