title: Alteration of autophagosomal proteins (LC3, GABARAP and GATE-16) in Lewy body disease.
abstract: Macroautophagy is a dynamic process whereby cytoplasmic molecules are sequestered within autophagosomes. Based on amino acid similarity, there exist two groups of mammalian autophagy-related gene (Atg) 8 homologues [microtubule-associated protein 1 light chain 3 (LC3) and γ-aminobutyric-acid type A receptor associated proteins (GABARAPs)], which play essential role in autophagosomal formation. Despite recent progress in studies on LC3, the other Atg8 homologues remain to be poorly understood, especially in pathological condition. In this study, we determined whether Atg8 homologues are affected in Lewy body disease, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Our findings indicated that biochemical and pathological properties of LC3 were altered and that the level of LC3 was increased in an insoluble fraction from the brain of patients with DLB, whereas the level of GABARAPs was decreased in DLB. Furthermore, immunohistochemical staining revealed that both LC3 and GABARAPs were localized in Lewy bodies in PD and DLB. These findings suggest that autophagic function is impaired through alteration of Atg8 homologues in Lewy body disease.
authors.affiliation: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. kunikazu@cc.hirosaki-u.ac.jp
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Mori
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D000071190:Autophagy-Related Protein 8 Family; D002458:Cell Fractionation / Q000379:methods; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D000071456:Sequestosome-1 Protein; D012995:Solubility
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; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein