Alteration of autophagosomal proteins in the brain of multiple system atrophy

作者：Tanji Kunikazu^*; Odagiri Saori; Maruyama Atsushi; Mori Fumiaki; Kakita Akiyoshi; Takahashi Hitoshi; Wakabayashi Koichi

来源：Neurobiology of Disease, 2013, 49: 190-198.

DOI：10.1016/j.nbd.2012.08.017

• Autophagy
• GABARAP
• GATE-16
• Glial cytoplasmic inclusion
• LC3
• Lysosome
• Multiple system atrophy
• Oligodendrocyte

Autophagosomal formation is an initial step for macroautophagy. Similar to the yeast autophagy-related gene 8 (ATG8), mammalian ATG8 is responsible for autophagosomal formation, and categorized into LC3 and GABARAPs/GATE-16. Recent studies have shown that impairment of the autophagy-lysosome system is associated with formation of cytoplasmic inclusions observed in various neurodegenerative disorders including Parkinson%26apos;s disease (PD) and dementia with Lewy bodies (DLB). Although abnormal alpha-synuclein accumulation is a cardinal neuropathological feature in PD, DLB and multiple system atrophy (MSA), it is unclear whether autophagy is altered in MSA. We here demonstrated that the level of matured GABARAPs was significantly decreased in the cerebellum of MSA relative to controls, and that the higher levels of matured and lipidated LC3 were detected in detergent-insoluble fraction of MSA. Immunohistochemical analysis showed that the vast majority of glial cytoplasmic inclusions, a hallmark of MSA, were positive for LC3, whereas they were unstained or barely stained with anti-GABARAPs or anti-GATE-16 antibodies. Our data suggest that autophagy maturation is impaired through the repressed levels of autophagosomal proteins in MSA.

• 出版日期2013-1