ANNOUNCEMENTS
Amyotrophic Lateral Sclerosis (ALS) is a lethal, progressive neurodegenerative disorder caused by death of the motor neurons in the cortex, brain and the spinal cord characterized by weakening of muscles due to inability of the motor neurons to send signals to the brain resulting in atrophy making it harder to walk, talk and breathe which eventually leads to death. Few of the cases of ALS are associated with transfer of genes from either of the parents following autosomal pattern of inheritance called familial ALS while most of the others don’t have any definite cause and may occur through putative environmental and age-dependent risk factors called sporadic ALS. Mutations in SOD1, TARDBP, FUS, C9orf72 and several other genes are known to be the reason behind ALS. Glutamate excitotoxicity, mitochondrial dysfunction, microglial abnormality, oxidative stress etc. are also the possible causes of ALS. Here, we try to understand the complex protein-protein interaction network of ALS using network theory, an approach to understand the dynamics of biological system using mathematical representations (graph theory). When the topological properties governing the structure and behavior of network were analyzed, ALS network was found be hierarchical scale- free, the one in which modules regulate the network preferably than hubs. The unpredictable popularity of the hubs also signifies network’s disassortative nature. Knocking down of the leading hubs does not breakdown the network, moreover, enhances its modular regulation capability. However, key regulators are few of the leading hubs, present at each modular level, starting from main network to the motif level. They are deeply rooted as the backbone of the network, playing a significant role in regulating the network. EED among the key regulators is the most important one as it is present among top 50 leading hubs. The removal of these key regulators from the network may result in network breakdown.
Keywords: Amyotrophic Lateral Sclerosis (ALS), network theory, modules, hubs, key regulators, knock-out
