Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 408, Issue 1-2, Pages 37-46Publisher
SPRINGER
DOI: 10.1007/s11010-015-2480-5
Keywords
Alzheimer's disease; Amyloid-beta; Beta-site amyloid precursor protein cleaving enzyme 1; GW7647; Peroxisome proliferator-activated receptor alpha; Phosphoinositide 3-kinase
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Funding
- Science and Technology Research Project of Chongqing Municipal Education Commission [KJ1400227]
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Alzheimer's disease is a neuroinflammatory disease and is the most common cause of dementia in the elderly. Studies have shown the beneficial effects of the peroxisome proliferator-activated receptor alpha (PPAR-alpha) agonists on the treatment of neuroinflammatory diseases. The aim of the present study is to examine the ability of GW7647 (a PPAR-alpha agonist) to regulate amyloid precursor protein (APP) amyloidogenic processing in human neuroblastoma SH-SY5Y cells transfected with APPswe gene. After administration of GW7647 for 24 h, the levels of APP, soluble APP beta (sAPP beta), and presenilin 1 (PS-1) were assessed by Western blot. Cellular culture medium levels of amyloid-beta 42 (A beta 42) were analyzed by ELISA, and the activity of beta-site APP cleaving enzyme 1 (BACE-1) was measured by fluorometric assay. We found that GW7647 decreased the expression of sAPP beta and the activity of BACE-1, and also reduced A beta 42 release. However, GW7647 did not modify the levels of APP and PS-1. Furthermore, LY294002, the phosphoinositide 3-kinase (PI3-K) inhibitor, reversed the effects of GW7647 on the BACE-1 activity and the levels of sAPP beta and A beta 42. Our data demonstrate that GW7647 may reduce A beta production via inhibiting BACE-1 activity, and this may involve in PI3-K pathway.
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