The ‘Omics’ of Amyotrophic Lateral Sclerosis

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. 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. 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. a potent inducer of neovascularization that has a role in ribosomal RNA biogenesis, protein translation, and cell growth. a nitrogenous organic acid that helps provide energy to cells by increasing the synthesis of ATP. a subunit of a neuron-specific chromatin-remodeling complex that can also be associated with FUS and plays a role in dendritic length regulation. this protein is expressed in many regions of the brain, localizes to the cytoplasm of neurons, and seems to have a role in membrane trafficking. this protein is part of the dynactin complex that is essential for neuronal function (vesicle motility along the axons). Mutations in this gene are considered to be potential susceptibility factors for ALS. Three heterozygous nucleotide transitions leading to missense mutations have been detected in three cases of fALS and in one case of sALS. in the earlier stages of ALS, this refers to the loss of axons of motor neurons, commencing at the neuromuscular junction, before neuronal cell bodies are affected in the spinal cord or brain. the study of stable or temporal changes in the genome, but not in the nucleotide sequence, that can influence the transcription pattern of a cell. a technique based on high-throughput DNA sequencing of exons exclusively (exons represent 1% of the human genome). this protein is involved in RNA transcription, splicing, and transport. It is a functional homolog of TDP43. a technique aimed at examining the whole genome in the search for genetic variants and evaluating whether these variants are associated with a given genetic trait or to a health condition. essential amino acid from which glutamate is synthesized. the most prominent excitatory neurotransmitter in the body. In ALS, the uncontrolled release of glutamate causes the excitotoxicity in motor neurons. HNRNPA1 and HNRNPA2B1 are essential for the assembly of ribonucleoprotein granules. may be defined as the study of metabolite profiles: the set of low molecular weight compounds produced by metabolic pathways, of a given cell, tissue, biofluid, organ, or organism at a given timepoint. a neuron originating from the motor region of the cerebral cortex. The neuron body is located in the spinal cord and the axon projects outside to connect and control muscles. the second most abundant metabolite in the CNS. It is a derivative of aspartic acid. the third most relevant neurotransmitter in the nervous system. It consists of NAA and glutamine residues coupled via peptide bonds. the tail of NEFH is composed of the repeating KSP motif (lysine, serine, proline). It plays an essential role in axon structure. Several mutations are known that affect the structure of the KSP motif, and multiple copies of the motif in both sALS and fALS cases prevent its proper function. synapse connecting the nervous and muscular systems. It is located between the synaptic end-bulbs of the motor neuron and the motor end-plate of the muscle fiber. helps in Golgi complex maintenance and is involved in vesicle trafficking and cellular morphogenesis. is crucial for the conversion of monomeric globular actin to fibrillary actin that forms the cell cytoskeleton. this protein has a potential role in DNA repair and RNA processing. involves the analysis of the whole repertoire of genes for a given organism (while functional genomics involves the study of the products of the gene repertoire). an antioxidant enzyme that metabolizes superoxide radicals. is involved in RNA biogenesis and in the regulation of gene expression and splicing. among other functions, this 2-aminoethanesulfonic acid is considered a neurotransmitter with protective properties against excitotoxicity exerted by glutamate, decreasing calcium entrance into the motor neuron. this gene encodes a cation channel with serine/threonine kinase activity. In a study in the western Pacific geographic region a threonine 1482 to isoleucine mutation was linked to ALS. However, another study in Japan did not find any association between fALS and this mutation. regulates the degradation of ubiquitinated proteins. is essential for the maturation of ubiquitin-containing autophagosomes. an intracellular membrane protein that associates with microtubules and facilitates protein transport through the membrane.