%0 Journal Article
%T Effects of Heparin and Enoxaparin on APP Processing and A¦Â Production in Primary Cortical Neurons from Tg2576 Mice
%A Hao Cui
%A Amos C. Hung
%A David W. Klaver
%A Toshiharu Suzuki
%A Craig Freeman
%A Christian Narkowicz
%A Glenn A. Jacobson
%A David H. Small
%J PLOS ONE
%D 2011
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0023007
%X Background Alzheimer's disease (AD) is caused by accumulation of A¦Â, which is produced through sequential cleavage of ¦Â-amyloid precursor protein (APP) by the ¦Â-site APP cleaving enzyme (BACE1) and ¦Ã-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower A¦Â plaque deposition and improve cognitive function in AD transgenic mice. Methodology/Principal Findings We examined whether heparin and enoxaparin influence APP processing and inhibit A¦Â 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 (sAPP¦Á, C99, C83 and A¦Â) 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 sAPP¦Á and A¦Â secretion. Heparin also decreased the level of ¦Â-secretase (BACE1) and ¦Á-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 ¦Á- and ¦Â-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0023007