The essential and downstream common proteins of amyotrophic lateral sclerosis: A protein-protein interaction network analysisReportar como inadecuado




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Amyotrophic Lateral Sclerosis ALS is a devastative neurodegenerative disease characterized by selective loss of motoneurons. While several breakthroughs have been made in identifying ALS genetic defects, the detailed molecular mechanisms are still unclear. These genetic defects involve in numerous biological processes, which converge to a common destiny: motoneuron degeneration. In addition, the common comorbid Frontotemporal Dementia FTD further complicates the investigation of ALS etiology. In this study, we aimed to explore the protein-protein interaction network built on known ALS-causative genes to identify essential proteins and common downstream proteins between classical ALS and ALS+FTD classical ALS + ALS-FTD groups. The results suggest that classical ALS and ALS+FTD share similar essential protein set VCP, FUS, TDP-43 and hnRNPA1 but have distinctive functional enrichment profiles. Thus, disruptions to these essential proteins might cause motoneuron susceptible to cellular stresses and eventually vulnerable to proteinopathies. Moreover, we identified a common downstream protein, ubiquitin-C, extensively interconnected with ALS-causative proteins 22 out of 24 which was not linked to ALS previously. Our in silico approach provides the computational background for identifying ALS therapeutic targets, and points out the potential downstream common ground of ALS-causative mutations.



Autor: Yimin Mao , Su-Wei Kuo , Le Chen, C. J. Heckman, M. C. Jiang

Fuente: http://plos.srce.hr/



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