The role of viral infectious triggers in multiple system atrophy

Misfolded protein aggregates appear to be a common feature of several ageing-related neurodegenerative diseases. Parkinson's disease (PD) and Multiple System Atrophy (MSA) belong to the family of synucleinopathies which are characterized by alpha-synuclein protein deposits. Although most studies have focused on the central nervous system, there is increasing evidence that the pathological alpha-synuclein inclusions originate in the periphery, from where they propagate to the central nervous system via the nerves innervating these organs and subsequently spread throughout the brain. The origin of MSA is unknown in most cases, but it is believed to involve a combination of genetic and environmental factors. Recent evidence proposes that synucleinopathies could be triggered by infectious and/or inflammatory insults in the periphery causing alpha-synuclein to aggregate and spread towards the central nervous system. In this PhD project, the overall goal is to unravel the mechanism of these triggers in the pathogenesis of MSA. A better understanding of how synucleinopathies are triggered can contribute to disease prevention in disease diagnosis and the identification of potential new disease targets and the development of novel therapeutic strategies.