Research Update #1

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.

I also expanded the model on the role of adaptive immunity. In addition to the previous model, I added some other roles of T reg cells in protection of neurons cells by suppressing various routes of inflammatory responses. T reg cells keep ubiquitin proteasome system(UPS) functioning normally.  Diminished function of UPS can possibly lead to the aggregation of alpha synuclein and the formation of nitrated alpha synuclein. T reg cells also protect neurons by promoting expression of mitochondrial proteins. T reg cells also inhibit the transcription of cytokines by inhibiting the expression of NF-kB p65 subunit.  Nitrated alpha synuclein and many cytokines are proinflammatory agents. Elevated levels of such proinflammatory agents are considered to damage the dopaminergic neurons that may lead to neurodegeneration.

I hope to start working on Power Law Analysis and Simulation software(PLAS) next week. By using PLAS, reactions happening in environments around neurons will be described mathematically. After establishing the baseline model, diseased state will be established and compared to the baseline model.