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Computational Systems Analysis of Dopamine Metabolism
Computational Systems Analysis of Dopamine Metabolism
- Source :
- PLoS ONE, PLoS ONE, Vol 3, Iss 6, p e2444 (2008)
- Publication Year :
- 2008
- Publisher :
- Public Library of Science (PLoS), 2008.
-
Abstract
- A prominent feature of Parkinson's disease (PD) is the loss of dopamine in the striatum, and many therapeutic interventions for the disease are aimed at restoring dopamine signaling. Dopamine signaling includes the synthesis, storage, release, and recycling of dopamine in the presynaptic terminal and activation of pre- and post-synaptic receptors and various downstream signaling cascades. As an aid that might facilitate our understanding of dopamine dynamics in the pathogenesis and treatment in PD, we have begun to merge currently available information and expert knowledge regarding presynaptic dopamine homeostasis into a computational model, following the guidelines of biochemical systems theory. After subjecting our model to mathematical diagnosis and analysis, we made direct comparisons between model predictions and experimental observations and found that the model exhibited a high degree of predictive capacity with respect to genetic and pharmacological changes in gene expression or function. Our results suggest potential approaches to restoring the dopamine imbalance and the associated generation of oxidative stress. While the proposed model of dopamine metabolism is preliminary, future extensions and refinements may eventually serve as an in silico platform for prescreening potential therapeutics, identifying immediate side effects, screening for biomarkers, and assessing the impact of risk factors of the disease.
- Subjects :
- Levodopa
Parkinson's disease
Dopamine
In silico
lcsh:Medicine
Neuroscience/Neural Homeostasis
Substantia nigra
Striatum
Pharmacology
Biology
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Neuroscience/Theoretical Neuroscience
lcsh:Science
030304 developmental biology
0303 health sciences
Computational model
Multidisciplinary
lcsh:R
Computational Biology
medicine.disease
Corpus Striatum
3. Good health
Substantia Nigra
Oxidative Stress
lcsh:Q
Signal transduction
Neuroscience/Neurobiology of Disease and Regeneration
Pharmacology/Personalized Medicine
Neuroscience
030217 neurology & neurosurgery
Research Article
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....3b12bc5d909a1d4c32909b029111bc55
- Full Text :
- https://doi.org/10.1371/journal.pone.0002444