Effects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mice.

<h4>Background</h4>Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan...

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Autores principales:	Hao Cui, Amos C Hung, David W Klaver, Toshiharu Suzuki, Craig Freeman, Christian Narkowicz, Glenn A Jacobson, David H Small
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eda00fd627b64d1b93cb1126837c49bd
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spelling	oai:doaj.org-article:eda00fd627b64d1b93cb1126837c49bd2021-11-18T06:48:58ZEffects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mice.1932-620310.1371/journal.pone.0023007https://doaj.org/article/eda00fd627b64d1b93cb1126837c49bd2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21829577/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice.<h4>Methodology/principal findings</h4>We examined whether heparin and enoxaparin influence APP processing and inhibit Aβ production in primary cortical cell cultures. Heparin and enoxaparin were incubated with primary cortical cells derived from Tg2576 mice, and the level of APP and proteolytic products of APP (sAPPα, C99, C83 and Aβ) was measured by western blotting. Treatment of the cells with heparin or enoxaparin had no significant effect on the level of total APP. However, both GAGs decreased the level of C99 and C83, and inhibited sAPPα and Aβ secretion. Heparin also decreased the level of β-secretase (BACE1) and α-secretase (ADAM10). In contrast, heparin had no effect on the level of ADAM17.<h4>Conclusions/significance</h4>The data indicate that heparin and enoxaparin decrease APP processing via both α- and β-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study.Hao CuiAmos C HungDavid W KlaverToshiharu SuzukiCraig FreemanChristian NarkowiczGlenn A JacobsonDavid H SmallPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e23007 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hao Cui Amos C Hung David W Klaver Toshiharu Suzuki Craig Freeman Christian Narkowicz Glenn A Jacobson David H Small Effects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mice.
description	<h4>Background</h4>Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice.<h4>Methodology/principal findings</h4>We examined whether heparin and enoxaparin influence APP processing and inhibit Aβ production in primary cortical cell cultures. Heparin and enoxaparin were incubated with primary cortical cells derived from Tg2576 mice, and the level of APP and proteolytic products of APP (sAPPα, C99, C83 and Aβ) was measured by western blotting. Treatment of the cells with heparin or enoxaparin had no significant effect on the level of total APP. However, both GAGs decreased the level of C99 and C83, and inhibited sAPPα and Aβ secretion. Heparin also decreased the level of β-secretase (BACE1) and α-secretase (ADAM10). In contrast, heparin had no effect on the level of ADAM17.<h4>Conclusions/significance</h4>The data indicate that heparin and enoxaparin decrease APP processing via both α- and β-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study.
format	article
author	Hao Cui Amos C Hung David W Klaver Toshiharu Suzuki Craig Freeman Christian Narkowicz Glenn A Jacobson David H Small
author_facet	Hao Cui Amos C Hung David W Klaver Toshiharu Suzuki Craig Freeman Christian Narkowicz Glenn A Jacobson David H Small
author_sort	Hao Cui
title	Effects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mice.
title_short	Effects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mice.
title_full	Effects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mice.
title_fullStr	Effects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mice.
title_full_unstemmed	Effects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mice.
title_sort	effects of heparin and enoxaparin on app processing and aβ production in primary cortical neurons from tg2576 mice.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/eda00fd627b64d1b93cb1126837c49bd
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Effects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mice.

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