Multiple System Atrophy

Abstract

Multiple system atrophy (MSA) is a rare, rapidly progressive and fatal neurodegenerative disorder. Its main clinical features include autonomic dysfunction and motor impairment, leading to death few years after clinical diagnosis. Pathologically, MSA is especially characterized by the presence of α-synuclein deposits in the cytoplasm of oligodendrocytes. In addition to the abnormal accumulation of α-synuclein, MSA patients develop neuroinflammation, demyelination, and neurodegeneration that seem to be associated with α-synuclein pathology. Thus, together with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), MSA is considered an α-synucleinopathy. The cause of MSA, how and why the pathology is triggered, remains unknown. However, clinical and preclinical studies conducted in the last years have helped to unravel different aspects of MSA that might play an essential role in its progression and that could be used as potential targets for disease modification. This chapter discusses the current understanding on MSA pathogenesis; the histopathological, cellular, and molecular changes underlying its clinical presentation; and the therapeutic approaches that have been or are currently conducted in an effort to slow down or halt disease progression.