A plethora of evidences associates structural dysfunction of the protein alpha-synuclein (aS) and self-assembly into filaments with the neuropathology of Synucleinopathies such as Parkinson disease (PD) and Multiple System Atrophy (MSA). The protein exhibits a high potential to form polymorphic fibrils. Consistently, high-resolution structural determination of aS fibrils has unveiled a variety of polymorphic structures of either in vitro fibrils or ex vivo fibrils extracted from the brain of patients. Recently, structural polymorphism of aS fibrils has been associated with distinct Synucleinopathies. Interestingly, a characteristic shared by all post-mortem aS filament structures is the presence of non-proteinaceous molecules in assembled aS, indicating that chemical ligands may be involved in the assembly of aS fibrils in patient’s brain. These evidences highlight the complexity of the aS aggregation process and emphasizes the importance of developing conditions that lead to a better understanding of the structural and molecular basis behind aS assembly. In this work we set-up an experimental model that replicates the disease specific structures of aS filaments extracted from patients with MSA. These kind of experimental models will be invaluable for gaining a better understanding of disease, and thus for developing safe and effective mechanism-based therapies.