The 'Omics' of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that primarily affects motor neurons and is accompanied by sustained unregulated immune responses, but without clear indications of the ultimate causative mechanisms. The identification of a diverse array of ALS phenotypes, a series of recently discovered mutations, and the links between ALS and frontotemporal degeneration have significantly increased our knowledge of the disease. In this review we discuss the main features involved in ALS pathophysiology in the context of recent advances in 'omics' approaches, including genomics, proteomics, and others. We emphasize the pressing need to combine clinical imaging with various different parameters taken from omics fields to facilitate early, accurate diagnosis and rational drug design in the treatment of ALS. ALS, or amyotrophic lateral sclerosis, is a progressive neurodegenerative disease that affects motor neurons. There is no cure for ALS. Although ALS is a brain disease closely related to Parkinson's, Alzheimer's, and Huntington's diseases, so far the complex descriptions of ALS-associated damage have not clarified the ultimate causative mechanisms.Current interventions are the result of unintentional discoveries or the non-specific application of cell-based therapies whose effects are not completely understood. However, research on ALS is currently thriving and the body of knowledge on the subject has increased remarkably in recent years.The emergence of functional immunomics for ALS from established omics technologies are opening new therapeutic avenues based on the smart manipulation of the immune system.Molecular imaging in the field of ALS is evolving. Thus, a combination of omics technologies and clinical imaging may very well be the key for breaking-down ALS.Financial support was provided by grants AI075285 and AI093903 from the US National Institutes of Health, RG4111A1 and JF2161-A-5 from the National Multiple Sclerosis Society, and PA0069 from the International Progressive MS Alliance (F.J.Q.), the Regional Ministry of Economy, Science and Innovation (P11-CTS-8161 to D.P.), the Regional Ministry of Health (PI13-575 to S.L.), the PAIDI Program from the Andalusian Government (CTS-677 to D.P.), and the Spanish Ministry of Economy and Competitiveness with FEDER co-funding (PI14-1600 to D.P.; SAF-2012-39720 and CP10-00527 to C.R.). D.C-H. holds a postdoctoral fellowship from CONACyT (Mexico). M.C-G. holds a PIF-University of Seville PhD fellowship.Peer Reviewe