Altered lipid levels provide evidence for myelin dysfunction in multiple system atrophy

摘要: Multiple system atrophy (MSA) is a rapidly-progressive neurodegenerative disease characterized by parkinsonism, cerebellar ataxia and autonomic failure. A pathological hallmark of MSA the presence α-synuclein deposits in oligodendrocytes, myelin-producing support cells brain. Brain pathology vitro studies indicate that myelin instability may be an early event pathogenesis MSA. Lipid major constituent (78% w/w) has been implicated dysfunction However, changes, if any, lipid level/distribution brain are unknown. Here, we undertook comprehensive analysis myelin. We quantitatively measured three groups lipids, sphingomyelin, sulfatide galactosylceramide, which all important integrity function, affected (under motor cortex) unaffected visual white matter regions. For most species were severely decreased (40–69%) but not matter. An distribution showed no significant shift fatty acid chain length/content with The decrease levels was concomitant increased expression. These data absolute levels, distribution, lipids altered MSA, provide evidence for pathology. propose dysregulation course trigger instability.