Computational model
Single-cell comprehensive biophysical model of SN pars compacta (Muddapu & Chakravarthy 2021)
Vignayanandam R Muddapu [12021]
Parkinson’s disease (PD) is caused by the loss of dopaminergic cells in substantia nigra pars compacta (SNc), the decisive cause of this inexorable cell loss is not clearly elucidated. We hypothesize that “Energy deficiency at a sub-cellular/cellular/systems-level can be a common underlying cause for SNc cell loss in PD.” Here, we propose a comprehensive computational model of SNc cell which helps us to understand the pathophysiology of neurodegeneration at subcellular-level in PD. We were able to show see how deficits in supply of energy substrates (glucose and oxygen) lead to a deficit in ATP, and furthermore, deficits in ATP are the common factor underlying the pathological molecular-level changes including alpha-synuclein aggregation, ROS formation, calcium elevation, and dopamine dysfunction. The model also suggests that hypoglycemia plays a more crucial role in leading to ATP deficits than hypoxia. We believe that the proposed model provides an integrated modelling framework to understand the neurodegenerative processes underlying PD.
  • Substantia nigra pars compacta DA cell Show Other
  • Neuron or other electrically excitable cell Show Other
  • Muddapu VR, Chakravarthy VS (2021) Show Other
  • Muddapu, Vignayanandam R. [vignan.0009 at] Show Other
  • Chakravarthy, Srinivasa V. [schakra at] Show Other
Muddapu, V. R. & Chakravarthy, V. S. Influence of Energy Deficiency on the Molecular Processes of Substantia Nigra Pars Compacta Cell for Understanding Parkinsonian Neurodegeneration - A Comprehensive Biophysical Computational Model. bioRxiv 2020.02.18.950337 (2020). doi:10.1101/2020.02.18.950337
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Last Time: 3/1/2021 5:11:22 PM
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