Mathematical model for alpha-synuclein molecular dynamics
2014
National and Kapodistrian University of Athens, Athens, Greece
Alpha-synuclein is involved in several pathologies and has been described to have a central role in Parkinson's disease. The profiles of expression of alpha-synuclein have been suggested to be correlated with familial and sporadic forms of the disease and result in the aggregation of fibrils in the form of Lewy bodies in neurons. However, there is a lack of understanding of the molecular mechanisms of alpha-synuclein that can lead to the prevention or to a potential cure of Parkinson's disease. Here, a mathematical biomolecular reactions model is developed to describe the molecular dynamics of intracellular alpha-synuclein. Furthermore, experimental data of alpha-synuclein overexpression is obtained using a human neuroblastoma cell line to validate the simulated data generated with this model. The results show that in three hypothetical intervention scenarios the model is capable of simulating the cell viability outcome that fits with experimental data. This new model allows predicting alpha-synuclein dynamics in newly generated scenarios to estimate the underlying mechanisms that lead to proteolysis deregulation. This opens new possibilities in the study of alpha-synuclein and provides researchers with a powerful tool to test hypotheses prior to experimental tests.
In silico modeling of the effects of alpha-synuclein oligomerization on dopaminergic neuronal homeostasis
Elias S Manolakos
Added on: 09-23-2021
[1] https://bmcsystbiol.biomedcentral.com/articles/10.1186/1752-0509-8-54[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
