From serendipity to rational drug design in brain disorders: in silico, in vitro, and in vivo approaches.

Abstract Prolonged life expectancy and stressful lifestyles have increased the risk of developing neurological disorders, including neurodegenerative and psychiatric illnesses. Despite obvious and immediate needs for effective treatment, drug discovery for neurological disorders has been largely serendipitous, whereas hypothesis-driven drug development programs have been remarkably poor. This may be partly due to insufficient knowledge of molecular mechanisms underlying disease pathophysiology, complex genetic and environmental risk factors, and oversimplified diagnostic criteria. Here, we review recent progress in cell type–specific investigations, bioinformatics analyses, and large reference databases, the integration of which, when combined with effective use of animal models, provides novel insights into disease mechanisms, suggests innovative drug development, and ultimately promises superior treatments for patients suffering from neurological disorders.