Deciphering complex mechanisms in neurodegenerative diseases: the advent of systems biology

Classical biological methods involving analyses of one or several genes have been the mainstay for studying the pathogenesis of neurodegenerative disorders. However, it has become clear that these diseases exhibit complex molecular interactions involving both host genomes and environmental determinants. Systems biology represents an integrated and deeper investigation of interacting biomolecules within cells or organisms. This approach has only recently become feasible as high-throughput technologies including cDNA microarrays, mass spectrometric analyses of proteins and lipids together with rigorous bioinformatics have evolved. Herein, we review recent developments from studies of systems biology applied to multiple sclerosis, Alzheimer's disease and HIV-associated dementia as three prototypic neurodegenerative disorders. Existing high-content data derived from clinically and experimentally derived neural tissues point to convergent pathways among these neurodegenerative disorders, which transcend descriptive studies to reach a more integrated understanding of disease pathogenesis and, in some instances, highlighting 'druggable' network nodes.