Using a Systems Biology Approach To Reveal a Common Molecular Signature Across Neurodegenerative Diseases

Becoming increasingly prevalent in recent years, the three major neurodegenerative diseases - Alzheimer’s (AD) Parkinson’s (PD), and Huntington’s (HD) - continue to avoid most attempts at treatment and early diagnosis. Operating under the same pathogenic umbrella of neuronal death, it stands to reason that these, and all other neurodegenerative diseases would share risk factors by virtue of their similar pathologies. The aim of this study is to analyze and compare the molecular signatures of the three neurodegenerative diseases, using a holistic approach, in order to uncover a common signature among them. To achieve this, three gene expression datasets are used, one for each disease. A molecular signature of each of the three neurodegenerative diseases is defined using system biology approaches. The resulting signatures are interrogated for any statistically significant overlap between the diseases at different genomic levels. The results of the overlap analysis point to common malfunctions in various autophagic, apoptotic, and mitophagic pathways. Locating a shared signature of the three diseases opens new avenues for drug repositioning across neurodegenerative diseases, offering novel ways of prevention and treatment and supporting future research toward precision medicine.