Network analysis of neurodegenerative disease highlights a role of toll-like receptor signaling

Despite significant advances in the study of the molecular mechanisms altered in the development and progression of
neurodegenerative diseases (NDs), the etiology is still enigmatic and the distinctions between diseases are not always entirely clear. We present an efficient computationalmethod based on protein-protein interaction network (PPI) tomodel the functional network of NDs. The aim of this work is fourfold: (i) reconstruction of a PPI network relating to the NDs, (ii) construction of an association
network between diseases based on proximity in the disease PPI network, (iii) quantification of disease associations, and (iv)
inference of potentialmolecularmechanisminvolved in the diseases.The functional links of diseases not only showed overlap with the traditional classification in clinical settings, but also offered new insight into connections between diseases with limited clinical
overlap. To gain an expanded view of the molecular mechanisms involved in NDs, both direct and indirect connector proteins
were investigated. The method uncovered molecular relationships that are in common apparently distinct diseases and provided important insight into the molecular networks implicated in disease pathogenesis. In particular, the current analysis highlighted the Toll-like receptor signaling pathway as a potential candidate pathway to be targeted by therapy in neurodegeneration.