Despite signi cant 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 e cient computational method based on protein-protein interaction network (PPI) to model the functional network of NDs. e 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) quanti cation of disease associations, and (iv) inference of potential molecular mechanism involved in the diseases. e functional links of diseases not only showed overlap with the traditional classi cation in clinical settings, but also o ered 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. e 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.

Network Analysis of Neurodegenerative Disease Highlights a Role of Toll-Like Receptor Signaling

Corrado Priami
2014-01-01

Abstract

Despite signi cant 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 e cient computational method based on protein-protein interaction network (PPI) to model the functional network of NDs. e 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) quanti cation of disease associations, and (iv) inference of potential molecular mechanism involved in the diseases. e functional links of diseases not only showed overlap with the traditional classi cation in clinical settings, but also o ered 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. e 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.
2014
Nguyen, Thanh-Phuong; Caberlotto, Laura; Morine, Melissa J.; Priami, Corrado
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/881751
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