Abstract
Multiple system atrophy (MSA) is one of the few neurodegenerative disorders where we have a significant understanding of the clinical and pathological manifestations but where the aetiology remains almost completely unknown. Research to overcome this hurdle is gaining momentum through international research collaboration and a series of genetic and molecular discoveries in the last few years, which have advanced our knowledge of this rare synucleinopathy. In MSA, the discovery of α-synuclein pathology and glial cytoplasmic inclusions remain the most significant findings. Families with certain types of α-synuclein mutations develop diseases that mimic MSA, and the spectrum of clinical and pathological features in these families suggests a spectrum of severity, from late-onset Parkinson’s disease to MSA. Nonetheless, controversies persist, such as the role of common α-synuclein variants in MSA and whether this disorder shares a common mechanism of spreading pathology with other protein misfolding neurodegenerative diseases. Here, we review these issues, specifically focusing on α-synuclein mutations.
Highlights
Multiple system atrophy (MSA) is a neurodegenerative movement disorder affecting around 1 in 20,000 people[1,2]
According to the presenting clinical features and predominant manifestations, MSA is usually categorised as MSA-like pathology underlies both cerebellar (MSA-C) or MSA-P, there can be mixed signs, and some patients present with autonomic features
Initial clues came from studying α-synuclein (SNCA) and the hallmark histopathology in the brains of patients with MSA: glial cytoplasmic inclusions (GCIs) that reside predominantly in oligodendrocytes, the post mortem identification of which is required for a definitive diagnosis
Summary
Faculty Reviews are written by members of the prestigious Faculty Opinions Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. Any comments on the article can be found at the end of the article
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