Cui, H and Hung, AC and Klaver, DW and Suzuki, T and Freeman, C and Narkowicz, C and Jacobson, GA and Small, DH, Effects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mice, PLoS One, 6, (7) Article e23007. ISSN 1932-6203 (2011) [Refereed Article]
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Official URL: http://www.plosone.org/article/info%3Adoi%2F10.137...
Background: Alzheimer’s disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of b-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.
Methodology/Principal Findings: 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.Conclusions/Significance: 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.
|Item Type:||Refereed Article|
|Research Division:||Medical and Health Sciences|
|Research Group:||Pharmacology and Pharmaceutical Sciences|
|Research Field:||Clinical Pharmacology and Therapeutics|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Neurodegenerative Disorders Related to Ageing|
|Author:||Cui, H (Mr Hao Cui)|
|Author:||Hung, AC (Dr Amos Hung)|
|Author:||Klaver, DW (Mr David Klaver)|
|Author:||Narkowicz, C (Dr Christian Narkowicz)|
|Author:||Jacobson, GA (Dr Glenn Jacobson)|
|Author:||Small, DH (Professor David Small)|
|Web of Science® Times Cited:||6|
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