Multiple system atrophy: genetic risks and alpha-synuclein mutations

• Published in: F1000 research Vol. 6; p. 2072
• Main Authors: Whittaker, Heather T, Qui, Yichen, Bettencourt, Conceição, Houlden, Henry
• Format: Journal Article
• Language: English
• Published: England Faculty of 1000 Ltd 2017; F1000 Research Limited; F1000 Research Ltd
• Subjects: Atrophy; Biomarkers; Brain research; Clinical trials; Dementia; Disease; Genes; Hypotheses; Inclusion bodies; Medical Genetics; Motor Systems; Movement Disorders; Mutation; Neurobiology of Disease & Regeneration; Neurodegeneration; Neurodegenerative diseases; Neurogenetics; Neurology; Neuromuscular diseases; Neuronal Signaling Mechanisms; Neuropathology; Pathology; Patients; Protein folding; Proteins; Review; Studies; Synuclein; MSA; multiple system atrophy; neurodegenerative disorders; α-synuclein
• ISSN: 2046-1402; 2046-1402
• DOI: 10.12688/f1000research.12193.1

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.