title: Alteration of autophagosomal proteins in the brain of multiple system atrophy.
abstract: 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's disease (PD) and dementia with Lewy bodies (DLB). Although abnormal α-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.
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: kunikazu@cc.hirosaki-u.ac.jp.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan; Department of Neuroanatomy, Cell Biology and Histology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Odagiri
authors.affiliation: Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maruyama
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Mori
authors.affiliation: Department of Pathological Neuroscience, Center for Bioresource-based Researches, Brain Research Institute, University of Niigata, Niigata 951-8585, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata 951-8585, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D000071190:Autophagy-Related Protein 8 Family; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000071190:Autophagy-Related Protein 8 Family; C116741:GABARAP protein, human; C498698:GABARAPL2 protein, human; C477012:MAP1LC3A protein, human; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger