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Background

Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown aetiology characterised by the accumulation of insoluble α-synuclein (α-syn) aggregates in the cytoplasm of myelin-producing oligodendrocytes. Dysfunction of the lipid-rich myelin membrane may precede α-syn pathology in MSA pathogenesis. ATP-binding cassette transporter A8 (ABCA8) is a little-studied lipid transporter, which has recently been found to be highly expressed in oligodendrocyte-rich white matter regions of the human brain. ABCA8 expression promotes sphingomyelin production in oligodendrocytes in vitro, suggesting a role in myelin formation and maintenance.

Objective

We hypothesise that aberrant ABCA8 expression in oligodendrocytes plays a role in the early pathogenesis of MSA by impacting myelin stability and regulation of α-syn and p25α.

Methods

We measured the expression of ABCA8, α-syn and p25α in MSA brains in disease-affected grey matter (GM, putamen and cerebellum), disease-affected white matter (WM, under the motor cortex) and an unaffected brain region (visual cortex). We transfected human oligodendrocytes with ABCA8 and assessed its impact on α-syn and p25α expression.

Results

ABCA8 expression was significantly increased in the disease-affected GM and WM with no significant change in the unaffected brain region. α-syn and p25α expression were significantly increased in the disease-affected WM and GM respectively. Overexpression of ABCA8 in oligodendrocytes caused significant increases in both α-syn and p25α expression.

Conclusions

These data suggest a direct relationship between the levels of ABCA8 and the ectopic expression of α-syn and increased expression of p25α. As these data reflect results found in MSA, we hypothesise that increased ABCA8 may precipitate MSA pathology."xsd:string
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http://purl.uniprot.org/citations/23948991http://purl.uniprot.org/core/author"Kim W.S."xsd:string
http://purl.uniprot.org/citations/23948991http://purl.uniprot.org/core/author"Halliday G.M."xsd:string
http://purl.uniprot.org/citations/23948991http://purl.uniprot.org/core/author"Hsiao J.H."xsd:string
http://purl.uniprot.org/citations/23948991http://purl.uniprot.org/core/author"Bleasel J.M."xsd:string
http://purl.uniprot.org/citations/23948991http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23948991http://purl.uniprot.org/core/name"J Parkinsons Dis"xsd:string
http://purl.uniprot.org/citations/23948991http://purl.uniprot.org/core/pages"331-339"xsd:string
http://purl.uniprot.org/citations/23948991http://purl.uniprot.org/core/title"Increased expression of ABCA8 in multiple system atrophy brain is associated with changes in pathogenic proteins."xsd:string
http://purl.uniprot.org/citations/23948991http://purl.uniprot.org/core/volume"3"xsd:string
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