Increased Expression of ABCA8 in Multiple System Atrophy Brain is Associated with Changes in Pathogenic Proteins

摘要: Background Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown aetiology characterised by the accumulation insoluble α-synuclein (α-syn) aggregates in cytoplasm myelin-producing oligodendrocytes. Dysfunction lipid-rich myelin membrane may precede α-syn pathology MSA pathogenesis. ATP-binding cassette transporter A8 (ABCA8) little-studied lipid transporter, which has recently been found to be highly expressed oligodendrocyte-rich white matter regions human brain. ABCA8 expression promotes sphingomyelin production oligodendrocytes vitro, suggesting role formation and maintenance. Objective We hypothesise that aberrant plays early pathogenesis impacting stability regulation p25α. Methods measured ABCA8, p25α brains disease-affected grey (GM, putamen cerebellum), (WM, under motor cortex) an unaffected brain region (visual cortex). transfected with assessed its impact on expression. Results was significantly increased GM WM no significant change region. were respectively. Overexpression caused increases both Conclusions These data suggest direct relationship between levels ectopic As these reflect results MSA, we precipitate pathology.