Current Synthetic and Systems Biology
Open Access
ISSN: 2332-0737
+44-77-2385-9429
ISSN: 2332-0737
+44-77-2385-9429
Sahil Doshi
Upper St. Clair High School, USA
Posters & Accepted Abstracts: Curr Synthetic Sys Biol
As the sixth-leading cause of death in the United States, Alzheimer�s disease (AD) has received significant attention as a neurodegenerative disease that needs an effective treatment option. In particular, oxidative stress has gained prominence for its emergence during the aging process and ability to activate inflammatory pathways. In order to simulate signaling pathway behavior accurately, a continuous time Markov chain (CTMC) is developed to include stochasticity of pathway behavior. Using the PRISM model checker, the c-Jun/JNK pathway is developed with oxidative stress as the input stimuli, and multiple transition routes within the pathway were added to include stochastic effects. Along with the signaling pathway, gene expression was also coded by developing modules for BACE1 transcription and protein production. Relating oxidative species concentration to kinase phosphorylation was achieved by using a variation of Michaelis-Menten kinetics; at extremely high concentrations of oxidative species, the concentration of phosphorylated kinases reaches a limiting value corresponding to the maximum number of kinases available for phosphorylation. After running the simulation for 650 seconds, several observations were made: at lower levels of oxidative stress for activating the pathway, because of the effects of the stochasticity, most of the results for varying inputs of oxidative stress stimuli resulted in a relatively same range of BACE1 mRNA transcripts and amyloid beta protein concentration. However, in the short run, higher amounts of oxidative species caused a more rapid phosphorylation of the signaling pathway, resulting in a faster increase of amyloid beta before steady state is reached.
Email: sahilbdoshi@aol.com