Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling

被引:28
作者
Coggan, Jay S. [1 ]
Bittner, Stefan [2 ]
Stiefel, Klaus M. [1 ]
Meuth, Sven G. [2 ]
Prescott, Steven A. [3 ,4 ,5 ]
机构
[1] NeuroLinx Res Inst, La Jolla, CA 92039 USA
[2] Univ Klinikum Munster, Inst Physiol, Dept Neurol, D-48149 Munster, Germany
[3] Hosp Sick Children, Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada
[4] Univ Toronto, Dept Physiol, Toronto, ON M5G 1X8, Canada
[5] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5G 1X8, Canada
基金
加拿大健康研究院;
关键词
myelin; demyelination; multiple sclerosis; neurodegenerative disease; computational model; drug discovery; MYELINATED NERVE-FIBERS; MEMBRANE PROPERTY ABNORMALITIES; DISTRIBUTED-PARAMETER MODEL; TUMOR-NECROSIS-FACTOR; MULTIPLE-SCLEROSIS; ACTION-POTENTIALS; EXCITABILITY PROPERTIES; ACCOMMODATIVE PROCESSES; CONDUCTION-VELOCITY; AXONAL EXCITABILITY;
D O I
10.3390/ijms160921215
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases.
引用
收藏
页码:21215 / 21236
页数:22
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