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Increased expression of ABCA8 in multiple system atrophy brain is associated with changes in pathogenic proteins
Jonathan M Bleasel1, Jen-Hsiang T Hsiao, Glenda M Halliday
1Neuroscience Research Australia, Sydney, NSW, Australia School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Journal of Parkinson'S Disease
|August 17, 2013
Summary
Increased ATP-binding cassette transporter A8 (ABCA8) expression in the brain may trigger Multiple System Atrophy (MSA) pathology. This is linked to elevated alpha-synuclein (α-syn) and p25α levels, impacting myelin stability.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Multiple system atrophy (MSA) is a fatal neurodegenerative disease linked to alpha-synuclein (α-syn) aggregation in oligodendrocytes.
- Oligodendrocyte dysfunction and myelin membrane integrity may precede α-syn pathology in MSA.
- ATP-binding cassette transporter A8 (ABCA8), a lipid transporter, is highly expressed in human brain white matter and promotes sphingomyelin production in oligodendrocytes.
Purpose of the Study:
- To investigate the role of aberrant ATP-binding cassette transporter A8 (ABCA8) expression in Multiple System Atrophy (MSA) pathogenesis.
- To determine if ABCA8 impacts myelin stability and the regulation of α-synuclein (α-syn) and p25α in oligodendrocytes.
- To explore the potential of ABCA8 as an early indicator or contributor to MSA.
Main Methods:
- Quantified ABCA8, α-synuclein (α-syn), and p25α expression in affected (grey matter, white matter) and unaffected (visual cortex) regions of Multiple System Atrophy (MSA) brains.
- Utilized human oligodendrocytes, transfecting them with ABCA8 to assess its direct impact on α-syn and p25α expression levels.
Main Results:
- Significantly elevated ABCA8 expression was observed in both disease-affected grey matter (GM) and white matter (WM) of MSA brains.
- α-synuclein (α-syn) and p25α expression levels were significantly increased in affected WM and GM, respectively.
- Overexpression of ABCA8 in human oligodendrocytes led to significant increases in both α-syn and p25α expression.
Conclusions:
- A direct correlation exists between elevated ABCA8 levels and the ectopic expression of α-synuclein (α-syn) and increased p25α.
- The findings suggest that increased ABCA8 expression may precipitate the pathological cascade observed in Multiple System Atrophy (MSA).
- ABCA8 warrants further investigation as a potential therapeutic target or biomarker for early MSA intervention.
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