Molecular target discovery for neural repair in the functional genomics era

Abstract

A comprehensive understanding of the molecular pathways activated by traumatic neural injury is of major importance for the development of treatments for spinal cord injury (SCI). High-throughput gene expression profiling is a powerful approach to reveal genome-wide changes in gene expression during a specific biological process. Microarray analysis of injured nerves or neurons would ideally generate new hypotheses concerning the progression or deregulation of injury- and repair-related biological processes, such as neural scar formation and axon regeneration. These hypotheses should subsequently be tested experimentally and would eventually provide the molecular substrates for the development of novel therapeutics. Over the last decade, this approach has elucidated numerous extrinsic (mostly neural scar-associated) as well as neuron-intrinsic genes that are regulated following an injury. To date, the main challenge is to translate the observed injury-induced gene expression changes into a mechanistic framework to understand their functional implications. To achieve this, research on neural repair will have to adopt the conceptual advances and analytical tools provided by the functional genomics and systems biology revolution. Based on progress made in bioinformatics, high-throughput and high-content functional cellular screening, and in vivo gene transfer technology, we propose a multistep "roadmap" that provides an integrated strategy for molecular target discovery for repair of the injured spinal cord.