caa a22 4500 60623537X CHVBK 20210128101242.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s11010-015-2480-5 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2480-5 PPAR-α agonist regulates amyloid-β generation via inhibiting BACE-1 activity in human neuroblastoma SH-SY5Y cells transfected with APPswe gene [Elektronische Daten] [Hua Zhang, Ying Gao, Pei-feng Qiao, Feng-li Zhao, Yong Yan] 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-α) agonists on the treatment of neuroinflammatory diseases. The aim of the present study is to examine the ability of GW7647 (a PPAR-α agonist) to regulate amyloid precursor protein (APP) amyloidogenic processing in human neuroblastoma SH-SY5Y cells transfected with APPswe gene. After administration of GW7647 for 24h, the levels of APP, soluble APPβ (sAPPβ), and presenilin 1 (PS-1) were assessed by Western blot. Cellular culture medium levels of amyloid-β 42 (Aβ42) 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 sAPPβ and the activity of BACE-1, and also reduced Aβ42 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 sAPPβ and Aβ42. Our data demonstrate that GW7647 may reduce Aβ production via inhibiting BACE-1 activity, and this may involve in PI3-K pathway. Springer Science+Business Media New York, 2015 Alzheimer's disease nationallicence Amyloid-β nationallicence Beta-site amyloid precursor protein cleaving enzyme 1 nationallicence GW7647 nationallicence Peroxisome proliferator-activated receptor alpha nationallicence Phosphoinositide 3-kinase nationallicence Aβ : Amyloid-β nationallicence AD : Alzheimer's disease nationallicence APP : Amyloid precursor protein nationallicence BACE-1 : Beta-site amyloid precursor protein cleaving enzyme 1 nationallicence PI3-K : Phosphoinositide 3-kinase nationallicence PPAR-α : Peroxisome proliferator-activated receptor alpha nationallicence PS1 : Presenilin 1 nationallicence sAPPβ : Soluble amyloid precursor protein beta nationallicence Zhang Hua Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, 400016, Chongqing, China aut Gao Ying Special Wards, The Affiliated Children's Hospital of Chongqing Medical University, 400014, Chongqing, China aut Qiao Pei-feng Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, 400016, Chongqing, China aut Zhao Feng-li Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, 400016, Chongqing, China aut Yan Yong Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, 400016, Chongqing, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 37-46 0300-8177 408:1-2<37 2015 408 11010 https://doi.org/10.1007/s11010-015-2480-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2480-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Hua Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, 400016, Chongqing, China aut NATIONALLICENCE 700 1- Gao Ying Special Wards, The Affiliated Children's Hospital of Chongqing Medical University, 400014, Chongqing, China aut NATIONALLICENCE 700 1- Qiao Pei-feng Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, 400016, Chongqing, China aut NATIONALLICENCE 700 1- Zhao Feng-li Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, 400016, Chongqing, China aut NATIONALLICENCE 700 1- Yan Yong Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, 400016, Chongqing, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 37-46 0300-8177 408:1-2<37 2015 408 11010