The role of peripheral immunity in Parkinson's Disease

In recent years the contraposition between inflammatory and neurodegenerative processes has been increasingly challenged. Inflammation has been emphasized as a key player in the onset and progression of Parkinson’s disease (PD) and other neurodegenerative disorders. Evidence of microglial activation, profound imbalance in phenotype and composition of peripheral immune cells, and impaired adaptive and innate immune responses, seem to contribute to the pathogenesis of the disease. Furthermore, peripheral inflammatory mechanisms and immunogenetic factors are likely to be implicated. Even though several lines of preclinical and clinical studies are supporting and defining the complex relationship between the immune system and PD, the exact mechanisms are currently unknown. The temporal and causal connections between innate and adaptive immune responses and neurodegeneration are unsettled as well, thus challenging our ambition to define an integrated and holistic model of the disease. Despite these difficulties, current evidence is providing the unique opportunity to develop immune-targeted approaches for PD, thus enriching our therapeutic armamentarium. This thesis provides an extensive overview of past and present studies that explored the implication of the immune system in neurodegeneration, thus paving the road for the concept of disease modification in PD.