Neuronetworks: Analysis of brain pathology in Mucopolysaccharidoses – A systems biology approach

Mucopolysaccharidoses (MPS) are rare lysosomal storage diseases characterized by defects in the activity of lysosomal hydrolases that degrade glycosaminoglycan, with progressive multisystemic involvement. Neurological damage is present in several MPS types. The relationship between the accumulation of glycosaminoglycans and the neurological disorder presented in these diseases remains unknown. For this purpose, we analyzed distinct types of MPS using publicly available transcriptomic data with a systems biology approach to search for clues about the pathophysiological mechanisms involved in the brain pathology of MPS. The most relevant proteins in the networks and ontology terms related to neurological damage in MPS were identified and compared among diseases. We performed the clustering analysis for GSE111906 (MPSI), GSE95224 (MPSII), GSE23075 (MPSIIIB), GSE15758 (MPSIIIB), and GSE76283 (MPSVII). Regarding biomarker discovery analysis, the top 10 genes were ranked according to the maximal clique centrality. Different ontologies were present in the different types of MPS. Ontologies were also present in all the MPS types, like axon guidance, Calcium signaling, PI3K-Akt signaling pathway, and Wnt signaling pathway. We hypothesize that these pathways are deranged because glycosaminoglycans play an essential role in the extracellular matrix composition, helping to regulate several processes. Systems biology approaches may help to understand the mechanisms of neuropathology in the different types of Mucopolysaccharidoses.