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Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells

AD (Alzheimer’s disease) is a neurodegenerative disease and the most common form of dementia. One of the pathological hallmarks of AD is the aggregation of extracellular Aβs (amyloid β-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction betw...

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Autores principales: Yanagisawa, Makoto, Ariga, Toshio, Yu, Robert K
Formato: Texto
Lenguaje:English
Publicado: American Society for Neurochemistry 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838405/
https://www.ncbi.nlm.nih.gov/pubmed/20305711
http://dx.doi.org/10.1042/AN20090063
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author Yanagisawa, Makoto
Ariga, Toshio
Yu, Robert K
author_facet Yanagisawa, Makoto
Ariga, Toshio
Yu, Robert K
author_sort Yanagisawa, Makoto
collection PubMed
description AD (Alzheimer’s disease) is a neurodegenerative disease and the most common form of dementia. One of the pathological hallmarks of AD is the aggregation of extracellular Aβs (amyloid β-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction between G(M1) ganglioside and Aβs. Several reports have documented the bifunctional roles of Aβs in NSCs (neural stem cells), but the precise effects of G(M1) and Aβ on NSCs have not yet been clarified. We evaluated the effect of G(M1) and Aβ-(1–40) on mouse NECs (neuroepithelial cells), which are known to be rich in NSCs. No change of cell number was detected in NECs cultured in the presence of either G(M1) or Aβ-(1–40). On the contrary, a decreased number of NECs were cultured in the presence of a combination of G(M1) and Aβ-(1–40). The exogenously added G(M1) and Aβ-(1–40) were confirmed to incorporate into NECs. The Ras–MAPK (mitogen-activated protein kinase) pathway, important for cell proliferation, was intact in NECs simultaneously treated with G(M1) and Aβ-(1–40), but caspase 3 was activated. NECs treated with G(M1) and Aβ-(1–40) were positive in the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay, an indicator of cell death. It was found that G(M1) and Aβ-(1–40) interacted in the presence of cholesterol and sphingomyelin, components of cell surface microdomains. The cytotoxic effect was found also in NSCs prepared via neurospheres. These results indicate that Aβ-(1–40) and G(M1) co-operatively exert a cytotoxic effect on NSCs, likely via incorporation into NEC membranes, where they form a complex for the activation of cell death signalling.
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spelling pubmed-28384052010-03-19 Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells Yanagisawa, Makoto Ariga, Toshio Yu, Robert K ASN Neuro Research Article AD (Alzheimer’s disease) is a neurodegenerative disease and the most common form of dementia. One of the pathological hallmarks of AD is the aggregation of extracellular Aβs (amyloid β-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction between G(M1) ganglioside and Aβs. Several reports have documented the bifunctional roles of Aβs in NSCs (neural stem cells), but the precise effects of G(M1) and Aβ on NSCs have not yet been clarified. We evaluated the effect of G(M1) and Aβ-(1–40) on mouse NECs (neuroepithelial cells), which are known to be rich in NSCs. No change of cell number was detected in NECs cultured in the presence of either G(M1) or Aβ-(1–40). On the contrary, a decreased number of NECs were cultured in the presence of a combination of G(M1) and Aβ-(1–40). The exogenously added G(M1) and Aβ-(1–40) were confirmed to incorporate into NECs. The Ras–MAPK (mitogen-activated protein kinase) pathway, important for cell proliferation, was intact in NECs simultaneously treated with G(M1) and Aβ-(1–40), but caspase 3 was activated. NECs treated with G(M1) and Aβ-(1–40) were positive in the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay, an indicator of cell death. It was found that G(M1) and Aβ-(1–40) interacted in the presence of cholesterol and sphingomyelin, components of cell surface microdomains. The cytotoxic effect was found also in NSCs prepared via neurospheres. These results indicate that Aβ-(1–40) and G(M1) co-operatively exert a cytotoxic effect on NSCs, likely via incorporation into NEC membranes, where they form a complex for the activation of cell death signalling. American Society for Neurochemistry 2010-03-15 /pmc/articles/PMC2838405/ /pubmed/20305711 http://dx.doi.org/10.1042/AN20090063 Text en © 2010 The Author(s). http://creativecommons.org/licenses/by-nc/2.5/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yanagisawa, Makoto
Ariga, Toshio
Yu, Robert K
Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells
title Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells
title_full Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells
title_fullStr Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells
title_full_unstemmed Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells
title_short Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells
title_sort cytotoxic effects of g(m1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838405/
https://www.ncbi.nlm.nih.gov/pubmed/20305711
http://dx.doi.org/10.1042/AN20090063
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