title: Effects of conjugated linoleic acid on cleavage of amyloid precursor protein via PPARγ.
abstract: Conjugated linoleic acid (CLA) plays important roles in physiological conditions. The aim of present study was to explore the effects of CLA on the cleavage of amyloid precursor protein (APP) and the potential mechanism involved. The effects of CLA on intracellular APP, BACE1 (β-site APP Cleaving Enzyme1, BACE1), a disintegrin and metalloprotease (ADAM10) and extracellular sAPPα (soluble) were analyzed by RT-PCR, Western blot and ELISA in SH-SY5Y cells. Our study indicated that CLA significantly decreased the expression of BACE1 and increased the extracellular secretion of sAPPα, but not affected the levels of APP and ADAM10. The study also revealed that the nuclear receptor peroxisome proliferators activated receptor γ (PPARγ) played an important role in the CLA-induced intracellular BACE1 decrease, as well as the extracellular sAPPα increase through knockdown of PPARγ transcription using siRNA. We hypothesize that CLA acts as an agonist or ligand, which binds with PPARγ and leads to the increase in APP cleavage via α-secretase-mediated pathway and the decrease in the deposition of Aβ.
authors.affiliation: School of Pharmaceutical Sciences, Rm 211, Sun Yat-sen University, 132 Waihuan East Road, Higher Education Mega Center, Guangzhou 510006, Guangdong, China.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Xian-Zi
authors.initials: XZ
authors.lastname: Wan
authors.forename: Xiang-Ling
authors.initials: XL
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhong
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D019787:Linoleic Acid; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human