Computational Modelling of TNFalpha Pathway in Parkinson's Disease (Sasidharakurup et al 2019)

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"The paper aims developing a computational framework of signaling using the principles of biochemical systems theory as a model for Parkinson’s disease. Several molecular interactions aided by TNFalpha, a proinflammatory cytokine play key roles in mediating glutamate excitotoxicity and neuroinflammation, resulting in neuronal cell death. In this paper, initial concentrations and rate constants were extracted from literature and simulations developed were based on systems of ordinary differential equations following first-order kinetics. In control or healthy conditions, a decrease in TNFalpha and neuronal cell death was predicted in simulations matching data from experiments, whereas in diseased condition, a drastic increase in levels of TNFalpha, glutamate, TNFR1 and ROS were observed similar to experimental data correlating diseased condition to augmented neuronal cell death. The study suggests toxic effects induced by TNFalpha in the substantia nigra may be attributed to Parkinson’s disease conditions."
1 . Sasidharakurup H, Nair L, Bhaskar K, Diwakar S (2020) Computational Modelling of TNFa Pathway in Parkinson’s Disease – A Systemic Perspective Complex Networks and Their Applications VIII. COMPLEX NETWORKS 2019. Studies in Computational Intell, Cherifi H, Gaito S, Mendes J, Moro E, Rocha L, ed.
Model Information (Click on a link to find other models with that property)
Model Type:
Brain Region(s)/Organism:
Cell Type(s):
Gap Junctions:
Transmitter(s): Glutamate;
Simulation Environment: CellDesigner;
Model Concept(s): Parkinson's; Signaling pathways;
Implementer(s): Diwakar, Shyam [shyam at];
Search NeuronDB for information about:  Glutamate;
Computational Modelling of TNFa Pathway in Parkinson’s Disease – A Systems Theory Perspective

This is the README for model published in the following paper:

Hemalatha Sasidharakurup, Nair, L., Bhaskar, K., and Dr. Shyam Diwakar, “Computational Modelling of TNFa Pathway in Parkinson’s Disease - A Systems Theory Perspective”, in Proceedings of the 8th international conference on Complex Networks and their Applications, Lisbon, Portugal, 2019.

A computational model of mapping TNFa signalling in Parkinson's disease(PD) has been
developed to understand how it mediates glutamate excitotoxicity and
neuroinflammation leading to disease pathogenesis and progression. Pathways were modeled and simulated using the 
biochemical pathway visualization program CellDesigner, a modeling tool for gene-regulatory 
and biochemical networks that support graphical notation and listing of symbols. The model allows 
a qualitative analysis of PD and a key signalling pathways for evaluating PD treatment conditions 
relating pathophysiology to molecular concentration changes recordable from biological

Last updated 03-April-2020
Developed by : Hemalatha Sasidharakurup, Lakshmi Nair, Kanishka Bhaskar & Shyam Diwakar    
Computational Neuroscience & Neurophysiology Lab, School of Biotechnology, Amrita Vishwa Vidyapeetham, India.

How to run the code

1. Download the given code and save the file in a folder.

2. Load the files in CellDesigner (

3. To reconstruct our graphs, copy and paste each pathway reactions into a new window in CellDesigner.

4. Set the initial values for each reactant as given in the paper.

5. Go to Simulations, select ControlPanel and click "execute" button to run the simulation.   
   A graph will be produced for each pathway.

6. One may have to rearrange the species in CellDesigner by dragging it manually, to have the look and feel of the pathway as shown in the paper.

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