Proteomics and network analysis identify common and specific pathways of neurodegeneration

Abstract

Neurodegenerative disorders, such as Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are multi-factorial in nature, involving several genetic mutations (in coding or regulatory regions) and epigenetic and environmental factors. The main clinical manifestation (movement disorders, cognitive impairment and/or psychiatric disturbances) depends on the neuron population being primarily affected. Complex and multifactorial neurodegenerative diseases can be investigated using a holistic approach that can give a global view about the pathogenetic process and shed light on specific and generic pathways of neurodegeneration. Proteomics offers a global molecular snapshot of proteins and consequently of processes that may influence neuronal death. The proteome in fact provides a dynamic view of what is happening in the system under investigation, because the expression of proteins, their abundance, their localization in tissues or cells, the type and amount of their post-translational changes depend from the environment and from the cellular physiological state. Therefore, all the projects presented in this thesis, by combining bioinformatics tools with proteomics, aimed at highlighting biochemical processes shared by different neurodegenerative diseases and diseasespecific pathways, which may justify the degeneration of dopaminergic neurons in PD. Finally, a focus on the mitochondrial interactome and proteome intended to elucidate important specific steps of the degenerative process in PD