Advanced glycation end products enhance amyloid precursor protein expression by inducing reactive oxygen species.
Accumulation of senile plaques comprising Abeta and neurofibrillary tangles is a major hallmark in the brain of AD patients. Ample evidence has shown that inflammation and reactive oxygen species (ROS) increase in the AD patient's brain. However, the pathogenesis of AD is unclear. Some risk factors of AD include age, sex, genetics, and chronic disease. Epidemiological studies have suggested that the levels of advanced glycation end products (AGEs) are enhanced in patients with diabetes mellitus and during the aging process. At the same time, evidence indicates a moderately increased risk of development of AD in diabetic patients. AGEs may play a role in the pathogenesis of AD. In this study, we proposed that amyloid precursor protein (APP) expression was regulated by AGEs. Our data showed that APP was up-regulated by AGEs in vitro and in vivo, and pretreatment of cells with an ROS inhibitor (N-acetyl-L-cysteine) blocked the effects of AGEs. In conditioned medium, the level of Abeta(1-42) increased after AGE treatment. Furthermore, the combination of AGEs and aggregated Abeta(1-42) increased ROS production and decreased cell viability. We suggest that AGEs participate in AD development and are an important risk factor in the pathogenesis of AD.
Ko
Shun-Yao
SY
Graduate Institute of Medical Science, Chang Jung Christian University, Kway Jen, Tainan, Taiwan. syko@mail.cjcu.edu.tw
Lin
Yi-Pai
YP
Lin
Yi-Shiuan
YS
Chang
Shu-Shing
SS
D000111:Acetylcysteine / Q000494:pharmacology; D000544:Alzheimer Disease / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D017127:Glycation End Products, Advanced; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D000111:Acetylcysteine