title: Role of transcriptional control in multiple system atrophy.
abstract: Multiple system atrophy (MSA) is an α-synucleinopathy that is clinically characterized by varying degrees of parkinsonian, autonomic, and cerebellar features. Unlike other α-synucleinopathies such as Parkinson's disease, MSA is unique in that the principal α-synuclein lesions, called glial cytoplasmic inclusions, occur in oligodendroglia rather than neurons, with significantly more α-synuclein accumulating in MSA brain compared with Parkinson's disease. Although well defined clinically, the molecular pathophysiology of MSA has barely been investigated. In particular, there have been no systematic studies of the perturbation of the brain transcriptome during the onset and progression of this disease. Interestingly, measurements of α-synuclein gene (SNCA) expression in MSA brain tissue have not revealed overexpression of this gene in oligodendroglia or neurons. It has therefore become clear that other genes and gene networks, both directly as noncoding RNAs or through protein products, contribute to the accumulation of the α-synuclein protein in the brain. This review provides a summary of current developments in the investigation of the transcriptional causes of MSA and outlines perspectives for future research toward the elucidation of the molecular pathology of MSA-specific neurodegeneration.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: James D
authors.initials: JD
authors.lastname: Mills
authors.affiliation: Neuroscience Research Australia, Sydney, New South Wales, Australia; School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia. Electronic address: m.janitz@unsw.edu.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Janitz
mesh_terms: D001921:Brain / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D019578:Multiple System Atrophy / Q000235:genetics* / Q000473:pathology; D009836:Oligodendroglia / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated; D014158:Transcription, Genetic / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D022661:RNA, Untranslated; D051844:alpha-Synuclein
keywords: Gene regulation; Multiple system atrophy; Neurodegenerative diseases; Transcriptome; α-Synuclein