Models and modeling systems in Alzheimer disease drug discovery

The rapid pace of neurobiology research has increased the prospects of developing drugs to prevent neurodegenerative disorders. Although the goal of delaying the onset of brain disorders may be within the grasp of modem medicine, there are several critical barriers to progress. Among these is the lack of appropriate models and modeling systems for specific neurodegenerative diseases. Traditionally, in drug discovery, testing, and development, a combination of models is used. These include in vitro, in vivo, transgenic, and other animal models. However, each of these models has limitations. In this article, the author advocates the use of "in silico" modeling systems, which could complement currently available models and enable investigators to simulate alternative strategies to modulate neural function in a dynamic interactive mode. Advances in computer technology, including increasing speed and memory, and ready access to parallel processing systems have made it easier for investigators to develop databases for computer abstractions of neural function and dysfunction and to begin to develop prototypes for use in complex systems modeling environments. Multimodeling systems have been widely used in other areas of science to study emergent behavior of complex systems, such as the impact of atmospheric changes on weather, flight patterns of birds in a flock, and the behavior of traders in a commodities market. Adoption of such approaches should increase understanding of the complexities of signal transduction pathways in neural networks and accelerate the drug discovery process.