Using systems biology and mathematical modeling approaches in the discovery of therapeutic targets for spinal muscular atrophy

TitleUsing systems biology and mathematical modeling approaches in the discovery of therapeutic targets for spinal muscular atrophy
Publication TypeJournal Article
Year of Publication2018
AuthorsButchbach, M. E. R.
JournalAdvances in neurobiology
Volume21
Pagination267-281
Date Published2018
ISSN2190-5215
KeywordsDrug Discovery; Gene Expression; Humans; Mathematical modeling; Models, Theoretical; Molecular Targeted Therapy; Motor Neurons; Muscular Atrophy, Spinal; Ordinary differential equations; SMN2; Spinal muscular atrophy; Survival of Motor Neuron 2 Protein; Systems Biology
Abstract

Systems biology uses a combination of experimental and mathematical approaches to investigate the complex and dynamic interactions with a given system or biological process. Systems biology integrates genetics, signal transduction, biochemistry and cell biology with mathematical modeling. It can be used to identify novel pathways implicated in diseases as well as to understand the mechanisms by which a specific gene is regulated. This review describes the development of mathematical models for the regulation of an endogenous modifier gene, SMN2, in spinal muscular atrophy-an early-onset motor neuron disease that is a leading genetic cause of infant mortality worldwide-by cAMP signaling. These mathematical models not only can aid in understanding how SMN2 expression is regulated but they can also be used to examine the best ways to manipulate cAMP signaling to maximally increase SMN2 expression. These models will lead to the development of therapeutic strategies for treating SMA. This systems biology approach can also be applied to other neurological diseases, particularly those in which a disease-causing gene or a modifier gene has been identified.

DOI10.1007/978-3-319-94593-4_10
Alternate JournalAdv Neurobiol
Refereed DesignationRefereed