**3. Transcriptional analysis in ALS**

In the last decade, the quantification of the transcriptome has represented one of the most informative research strategies for both discovering and defining mechanisms of pathogenesis in ALS as well as facilitating the discovery of biomarkers or new therapeutic approaches [24, 25]. In this regard, high-throughput genomic technologies, such as DNA microarrays, have been developed to simultaneously screen, on a genome-wide scale, the expression of thou‐ sands of genes in parallel in the same experiment, providing a more detailed picture of the ALS-related profile of molecular changes occurring during the disease progression [24, 26– 28]. Both ALS post-mortem tissues (e.g., brain, spinal cord, cerebrospinal fluid, and blood) and those taken from animal models have been investigated with this purpose, revealing the involvement of several cellular events into ALS pathobiology, including mitochondrial dysfunction, enhanced apoptosis, glutamate-mediated excitotoxicity, oxidative stress, protein misfolding/aggregation, abnormal calcium metabolism, and altered axonal transport and neuroinflammatory cascades [29, 30]. However, because of the inherent complexity of nervous tissue and the need for post-mortem material, the existing genomic studies of ALS were restricted to a limited number of post-mortem ALS samples (≤11 motor cortex and 14 spinal cord), which did not permit the inclusion of genome changes within a framework of pathways or networks [24, 26–28].
