Spinal cord molecular profiling provides a better understanding of amyotrophic lateral sclerosis pathogenesis

Research efforts in amyotrophic lateral sclerosis (ALS) have not yet provided a comprehensive explanation of the disease pathogenesis, which is emerging as a complex interaction between multiple factors. Gene expression studies traditionally based on single mRNA specie analysis have recently progressed to allow entire transcriptional profiles of affected tissues to be obtained through array-based methods. This experimental approach has significantly improved our understanding of the molecular changes occurring in ALS, although its limitations in the detection of low-abundance transcripts in tissues with a high level of complexity are becoming increasingly recognized. In this paper, experimental findings based on an expression study in post-mortem spinal cord from sporadic ALS individuals will be discussed in light of recently published data using array analysis in an animal model of the disease. Previous expression data obtained using conventional techniques are also compared. Through the analysis of the information arising from ALS post-mortem and animal model tissues studies, we have identified a pattern of molecular events in which factors implicated in the immune response, cytoprotection and growth-differentiation are differentially regulated in a time-dependent way from early to advanced stages of disease progression.