The effect of NAC and Carnosine on alzheimer’s disease-related in vitro model through RAGE-AGE signaling pathway

Abstract

Alzheimer’s disease (AD) is the most common dementia which found increasing with age. It involves neurodegeneration which leads to various abnormalities especially memory loss, inability to learn new things, lack of creativity, lack of decision making ability, lack of critical thinking, calculation inability, inability to live normal daily life, inability to recognize person, time and place, emotional disturbance, and difficulty to use language. Since AD has severe impact in various aspects on both the patients and their families, so we are interested to study the neurodegenerative mechanism when neuronal cells are under oxidative stress which will induce neuroinflammation through the binding of advanced glycation endproducts (AGEs) and its receptor (receptor for advanced glycation end products; RAGE) via NF-kB and MAPK signaling pathway and integration of oxidative stress. We found that upon exposure of the optimized AGEs, RAGE expression was increased. In response to this activation, accumulation of ROS was also enhanced. The activation of nuclear factor-kappa B (NF-κB) which is a primary transcription factor that plays an important role in regulating cellular responses was triggered. Hence, pro-inflammatory cytokines including IL1β, IL6 and TNFα were increased. In addition, increase in program cell death is likely to follow this activation. In this study, Fimbristylis ovata (F. ovata) (petroleum ether and methanol extract) 100 μg/mL was found to be able to reduce superoxide radical. Moreover, F. ovata (dichloromethane and methanol extract) 100 μg/mL, NAC, and Carnosine were found to decrease MAPK activation and cell apoptosis (p<0.05). In addition, F. ovata (petroleum ether, dichloromethane, and ethanol extract) and NAC were revealed to enhance NFκB translocation (p<0.05).