The commonality of protein interaction networks determined in neurodegenerative disorders (NDDs)

Motivation: Neurodegenerative disorders (NDDs) are progressive and fatal disorders, which are commonly characterized by the intracellular or extracellular presence of abnormal protein aggregates. The identification and verification of proteins interacting with causative gene products are effective ways to understand their physiological and pathological functions. The objective of this research is to better understand common molecular pathogenic mechanisms in NDDs by employing protein-protein interaction networks, the domain characteristics commonly identified in NDDs and correlation among NDDs based on domain information. Results: By reviewing published literatures in PubMed, we created pathway maps in Kyoto Encyclopedia of Genes and Genomes (KEGG) for the protein-protein interactions in six NDDs: Alzheimer's disease ( AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), dentatorubral-pallidoluysian atrophy ( DRPLA) and prion disease ( PRION). We also collected data on 201 interacting proteins and 13 compounds with 282 interactions from the literature. We found 19 proteins common to these six NDDs. These common proteins were mainly involved in the apoptosis and MAPK signaling pathways. We expanded the interaction network by adding protein interaction data from the Human Protein Reference Database and gene expression data from the Human Gene Expression Index Database. We then carried out domain analysis on the extended network and found the characteristic domains, such as 14-3-3 protein, phosphotyrosine interaction domain and caspase domain, for the common proteins. Moreover, we found a relatively high correlation between AD, PD, HD and PRION, but not ALS or DRPLA, in terms of the protein domain distributions. Availability: http://www.genome.jp/kegg/pathway/hsa/hsa01510.html ( KEGG pathway maps for NDDs) Contact: kanehisa@kuicr.kyoto-u.ac.jp