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Fenofibrate reduces amyloidogenic processing of APP in APP/PS1 transgenic mice via PPAR‐α/PI3‐K pathway
Author(s) -
Zhang Hua,
Gao Ying,
Qiao Peifeng,
Zhao Fengli,
Yan Yong
Publication year - 2014
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2014.10.004
Subject(s) - fenofibrate , amyloid precursor protein , genetically modified mouse , receptor , peroxisome proliferator activated receptor , chemistry , transgene , endocrinology , medicine , blot , presenilin , microbiology and biotechnology , biochemistry , alzheimer's disease , biology , gene , disease
The peroxisome proliferator‐activated receptor alpha (PPAR‐α), a member of the family of ligand‐activated nuclear hormone receptors, plays a relevant role in the development of Alzheimer's disease (AD). To better understand the role of PPAR‐α in AD, we examined the ability of fenofibrate (a PPAR‐α agonist) to regulate amyloid precursor protein (APP) processing in APP/PS1 transgenic mice. After intragastric administration of fenofibrate into 3‐month‐old APP/PS1 transgenic mice for 6 months, and the levels of relative proteins were quantified by quantitative reverse transcription‐PCR, Western blotting and ELISA. We found that fenofibrate increased the expression of PPAR‐α, and decreased beta‐site amyloid precursor protein cleaving enzyme 1 (BACE‐1) mRNA and protein levels, and also reduced soluble APPβ (sAPPβ) and amyloid‐β 42 (Aβ42) releases. However. fenofibrate did not modify the levels of APP and presenilin 1 (PS1). Furthermore, LY294002, the phosphoinositide 3‐kinase (PI3‐K) inhibitor, suppressed the effects of fenofibrate on BACE‐1, sAPPβ, and Aβ42, but not PPAR‐α. Our data suggest that fenofibrate may reduce the amyloidogenic processing of APP in APP/PS1 transgenic mice via PPAR‐α/PI3‐K pathway.