Multiple system atrophy (MSA) is a unique and fatal α-synucleinopathy associated with oligodendroglial inclusions and secondary neurodegeneration affecting striatum, substantia nigra, pons, and cerebellum. The pathogenesis remains elusive; however, there is emerging evidence suggesting a prominent role of neuroinflammation. Here, we critically review the relationship between αS and microglial activation depending on its aggregation state and its role in neuroinflammation to explore the potential of TNFα inhibitors as a treatment strategy for MSA and other neurodegenerative diseases.
Keywords: Disease-modifying treatment; Multiple system atrophy; Neurodegeneration; Neuroinflammation; TNFα; TNFα inhibitors.