I ran the diseased state of PD in PLAS on Thursday of week 7 and 8 and got some species showing ideal behavior that I expected. For example, the level of apoptosis was exponentially increased after increasing the amount of pro-inflammatory agents. But some species such as IL-beta exhibited odd behavior in diseased state. I expected it to be increased but it was decreased in the test. This may be due to the NF-kB model.
On Monday of Week 6, I struggled with fixing assigned values for constant rates so that species behave as expected in normal state. Some species still behaved oddly. It was due to my misunderstanding when I wrote equations on PLAS. So I had to go over whole cell designer and PLAS model to fix. I spent most of week 6 fixing that problem. It required lot of time to examine whole model.
I spent the fourth week of June finish establishing the baseline PLAS model. It was a simple work but was tedious and the work required few hours to finish writing flux equations and systems equations. To run the model in PLAS program better, there were minor changes removing few unnecessary reactions to simplify the model.
I spent third week of June developing a baseline PLAS model of inflammation in PD for the systems. All the reactions in the cell model were tagged before writing flux equations and systems equations. After sorting out all the species into dependent and independent variables, I started to write flux equations and systems equations for each reaction. There were some minor changes in the cell model.
I spent my second week establishing a model using CellDesigner on how nuclear receptor related 1 protein (Nurr1) inhibits inflammatory response. Nurr 1 is known to play a key role in the maintenance of the dopamiergic neurons. Nurr1 inhibits inflammatory response by inhibiting transcription of gene of cytokines through transrepression. Nurr1 binds to activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) that is binded to promoter region of the gene and attracts CoREST repressor complex. CoREST repressor complex binds to Nurr1 and CoREST repressor complex. Nurr1 complex inhibits transcription of cytokine genes by breaking down NF-kB complex into two subunits. These reactions happen both in nucleus of microglia and astrocytes. If there are no such transrepression, microglia release more cytokines that stimulate astrocytes to release cytokines amplifying the number of cytokines in the environment. Released cytokines interact with dopaminergic neurons hurting and leading them to the death pathway.