title: [Multiple system atrophy and autophagy].
abstract: Macroautophagy is a dynamic process whereby cytoplasmic molecules are sequestered within autophagosomes. There exist two groups of mammalian autophagy-related gene (Atg) 8 homologues (LC3 and GABARAPs), which play essential role in autophagosomal formation. We determined whether Atg8 homologues are affected in Lewy body disease (LBD) and multiple system atrophy (MSA). The level of LC3 was increased in an insoluble fraction from the brain of patients with LBD, whereas the level of GABARAPs was decreased in LBD. The level of matured GABARAPs was significantly decreased in the cerebellum of MSA, and that the higher levels of matured and lipidated LC3 were detected in detergent-insoluble fraction of MSA. Furthermore, immunohistochemical staining revealed that both LC3 and GABARAPs were localized in Lewy bodies and glial cytoplasmic inclusions in MSA were positive for LC3. These findings suggest that autophagic function is impaired through alteration of Atg8 homologues in LBD and MSA. Autophagy-enhancing strategies can therefore have therapeutic efficacy for various neurodegenerative diseases including LBD and MSA.
authors.affiliation: Department of Neuropathology, Hirosaki University School of Medicine.
authors.forename: Koichi
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D000071190:Autophagy-Related Protein 8 Family; D001921:Brain / Q000378:metabolism; D006801:Humans; D020961:Lewy Body Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008840:Microfilament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019578:Multiple System Atrophy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010588:Phagosomes / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000071190:Autophagy-Related Protein 8 Family; C116741:GABARAP protein, human; C430503:GABARAPL1 protein, human; C498698:GABARAPL2 protein, human; C477012:MAP1LC3A protein, human; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins