Protein-protein interactions network model underlines a link between hormonal and neurological disorders

Abstract

Gland and Hormonal Diseases (GHDs) constitute a class of non-communicable diseases that primarily results from either excessive or reduced secretion of hormones. Many of these diseases also have neurological manifestations. The need for their molecular understanding and subsequent effective drug target identification is paramount. Here, we have constructed Protein-Protein Interactions (PPI) networks by integrating intricate genomic and proteomic data available on various GHDs. From the network, hub proteins, key pathways, and gene ontologies were derived. The members of this network were then investigated for unraveling strong association with neurological disorders and a network of neurological disorder-associated genes was also constructed. Functional clusters in both the GHDs and neurological disorders were analyzed and compared. Based on our analyses, we have identified CBS, GJB2, KCNJ10, ERCC6, IGF1, HFE, GJB2, SOX2, SOX4, NTRK1, SOX9, BRCA1 and ERCC4 as common players in GHDs and neurological disorders. Hub proteins of GHDs include IGF1, TGFB1, JUN, and SMAD3 and those of neurological disorders include INS and IL6. These proteins could be considered as potential biomarkers. Our analysis suggest that perturbations in DNA damage repair, glucocorticoid hormone metabolism, interferon gamma mediated signaling pathway, and immune system regulation might promote GHDs while oxidative stress can do the same for neurological disorders. TGFB1 and SMAD3 agonists possess therapeutics potential against Alzheimer's disease. HLA-DRB1, HLA-DQB1 and TNF might have special role in either type of diseases. This study will pave the way for identification of biomarkers, drug targets and provide explanations regarding molecular and immunological pathogenesis in GHD-induced neurological disorders.

Keywords

• Endocrine disorders
• Neurological disorders
• Systems biology
• Biomarkers
• HLA-DRB1