Small molecule intervention in microtubule-associated human disease
1McKusick-Nathans Institute of Genetic Medicine and 2Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD 21205, USA
* To whom correspondence should be addressed at: McKusick-Nathans Institute of Genetic Medicine, 533 Broadway Research Building, 733 N. Broadway, Baltimore, MD 21205, USA. Tel: +1 4105026660; Fax: +1 4105020697; Email: katsanis{at}jhmi.edu
Received June 30, 2005; Accepted July 20, 2005
Microtubules are essential for a number of cellular processes that include the transport of intracellular cargo or organelles across long distances and the assembly of the mitotic spindle. The identification of numerous microtubule-associated proteins and the progressive elucidation of the mechanisms of microtubule assembly and transport are beginning to have a profound impact on the study and treatment of human genetic disease. A number of seemingly unrelated phenotypes have now been linked to microtubular dysfunction, especially in systems dependent heavily on microtubule-based transport, such as neurons and ciliated cells. In parallel, the association of microtubule transport defects with human genetic disease has led to the realization that targeting various aspects of microtubular biology with small molecules might offer new therapeutic paradigms, including the development of new therapeutic utility for seemingly old drugs. In this review, we discuss the use of small molecules in the investigation of microtubule-associated processes and particularly the screens of chemical compound libraries for the identification of lead compounds with potential utility in microtubule-associated disease processes.