The systems biology of neurofibromatosis type 1--critical roles for microRNA

Abstract

Neurofibromatosis type 1 (NF1) is one of the most common inherited neurological disorders with a wide range of clinical manifestations. The causative gene for NF1 encodes a multi-domain protein, neurofibromin, which interacts with RAS through its RAS-GAP domain. Dysfunction of neurofibromin results in abnormal RAS activation in the cells which has been thought to be the main process in the initiation and progression of NF1. Based on this hypothesis, inhibitors for various RAS mediated signaling pathways are in different stages of clinical trials to treat NF1 or NF1-associated symptoms. While the molecular genetics of NF1 has made significant progress in recent years, the underlying etiology and progression of NF1 are yet to be fully understood. Besides review and summarization of the latest results of genetic, transcriptomic and microRNA studies associated with NF1, we conducted limited post-hoc analysis to illustrate the importance of using integrated systems biology approach to study complex diseases like NF1.