Parkinson's disease: dopaminergic nerve cell model is consistent with experimental finding of increased extracellular transport of α-synuclein.

TitleParkinson's disease: dopaminergic nerve cell model is consistent with experimental finding of increased extracellular transport of α-synuclein.
Publication TypeJournal Article
Year of Publication2013
AuthorsBüchel F, Saliger S, Dräger A, Hoffmann S, Wrzodek C, Zell A, Kahle PJ
JournalBMC Neurosci
Volume14
Pagination136
PubMed Date11/2013
ISSN1471-2202
Keywordsalpha-Synuclein, Dopaminergic Neurons, Humans, Models, Neurological, Parkinson Disease
Abstract

BACKGROUND: Parkinson's disease is an age-related disease whose pathogenesis is not completely known. Animal models exist for investigating the disease but not all results can be easily transferred to humans. Therefore, mathematical or probabilistic models for the human disease are to be constructed in silico in order to predict specific processes within a cell, such as the dopamine metabolism and transport processes in a neuron.
RESULTS: We present a Systems Biology Markup Language (SBML) model of a whole dopaminergic nerve cell consisting of 139 reactions and 111 metabolites which includes, among others, the dopamine metabolism and transport, oxidative stress, aggregation of α-synuclein (αSYN), lysosomal and proteasomal degradation, and mitophagy. The predictive power of the model was investigated using flux balance analysis for the identification of steady model states. To this end, we performed six experiments: (i) investigation of the normal cell behavior, (ii) increase of O2, (iii) increase of ATP, (iv) influence of neurotoxins, (v) increase of αSYN in the cell, and (vi) increase of dopamine synthesis. The SBML model is available in the BioModels database with identifier MODEL1302200000.
CONCLUSION: It is possible to simulate the normal behavior of an in vivo nerve cell with the developed model. We show that the model is sensitive for neurotoxins and oxidative stress. Further, an increased level of αSYN induces apoptosis and an increased flux of αSYN to the extracellular space was observed.

Alternate JournalBMC Neurosci
PubMed ID24195591
PubMed Central IDPMC3871002
Cover Image: 

Location

Location

417 Powell-Focht Bioengineering Hall

9500 Gilman Drive La Jolla, CA 92093-0412

Contact Us

Contact Us

In Silico Lab:  858-822-1144

Wet Lab:  858-246-1625

FAX:   858-822-3120

Website Concerns: sbrgit@ucsd.edu

User Login