Amyotrophic Lateral Sclerosis (ALS) is a rare neurological disease affecting mainly motor neurons and often leads to paralysis and death in extreme cases. For exploring the role of microRNAs in genes regulation in ALS disease, miRanda was employed for prediction of target sites of miRNAs expressed in various parts of brain and CNS on 35 genes associated with ALS. Similar search was conducted using TargetScan and PicTar for prediction of target sites in UTR only. 1456 target sites were predicted using miRanda and more target sites were found in UTR and CDS region as compared to UTR. 11 target sites were predicted to be common by all the algorithms and, thus, these represent the most significant sites. Target site hotspots were identified and were recognized as hotspots for multiple miRNAs action, thus, acting as favoured sites of action for the repression of gene expression. The complex interplay of genes and miRNAs brought about by multiplicity and cooperativity was explored. This investigation will aid in elucidating the mechanism of action of miRNAs for the considered genes. The intrinsic network of miRNAs expressed in nervous system and genes associated with ALS may provide rapid and effective outcome for therapeutic applications and diagnosis. 1. Introduction A complete coordination of brain signals and their functional execution in different body parts is often found in multicellular organisms. However, mechanism underlying such coordination between brain and body is still a mystery. How a trivial defect in the coordinated communication can lead to a disease has been a subject of study for many years. Neurological disorders are responsible for major proportion of the global burden of disease [1]. The mammoth rise in incidence of neurological disorders has led to initiatives for declaration of global epidemic. With the significant rise in number of cases of neurological disorders across the globe, it is postulated that no particular geographical region or age group is immune to these disorders. Among these, neurodegenerative disorders that are triggered by environmental and genetic factors are major cause of concern for aged population. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, prion diseases, Amyotrophic Lateral Sclerosis, Huntington's disease, and various spinocerebellar ataxias account for significant morbidity. Progressive and slow degeneration of neurons as witnessed in these diseases leads to neuron dysfunction. The escalating cost of treatment and financial burden in terms of loss in disability adjusted life
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