Effects of conjugated linoleic acid on cleavage of amyloid precursor protein via PPARγ.

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.