title: Serine 403-phosphorylated p62/SQSTM1 immunoreactivity in inclusions of neurodegenerative diseases.
abstract: Protein inclusions in neurodegenerative diseases are associated with p62, which has an important role in autophagic clearance of polyubiquitinated proteins. Selective autophagy is regulated by S403-phosphorylation of p62, and S403-phosphorylated p62 (S403-phos-p62) accumulates in Atg5 conditional knockout (Atg5CKO) mice in which autophagosome formation is impaired. We performed immunohistochemical tests for the presence of S403-phos-p62 in postmortem brain of neurodegenerative disease cases, and found accumulations in amyotrophic lateral sclerosis and Alzheimer's disease tissues. In Atg5CKO and HD190QG (Huntington's disease model) mice, however, we found a postmortem decrease in S403-phos-p62 immunoreactivity, suggesting that post-mortem changes should be considered when interpreting human data.
authors: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama 351-0198, Japan; Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute, Saitama 351-0198, Japan; Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; CREST (Core Research for Evolutionary Science and Technology), JST, Tokyo 102-0076, Japan.
authors: Masaru
authors: M
authors: Kurosawa
authors: Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama 351-0198, Japan; Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute, Saitama 351-0198, Japan; CREST (Core Research for Evolutionary Science and Technology), JST, Tokyo 102-0076, Japan.
authors: Gen
authors: G
authors: Matsumoto
authors: Department of Neurology & Neuropathology, Tokyo Metropolitan Geriatric Hospital & Institute of Gerontology, Tokyo 173-0015, Japan.
authors: Hiroyuki
authors: H
authors: Sumikura
authors: Department of Neurology & Neuropathology, Tokyo Metropolitan Geriatric Hospital & Institute of Gerontology, Tokyo 173-0015, Japan.
authors: Hiroyuki
authors: H
authors: Hatsuta
authors: Department of Neurology & Neuropathology, Tokyo Metropolitan Geriatric Hospital & Institute of Gerontology, Tokyo 173-0015, Japan.
authors: Shigeo
authors: S
authors: Murayama
authors: Department of Cellular and Molecular Pharmacology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors: Takashi
authors: T
authors: Sakurai
authors: Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
authors: Tomomi
authors: T
authors: Shimogori
authors: Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors: Nobutaka
authors: N
authors: Hattori
authors: Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama 351-0198, Japan; Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute, Saitama 351-0198, Japan; CREST (Core Research for Evolutionary Science and Technology), JST, Tokyo 102-0076, Japan; Laboratory of Structural Neuropathology, Doshisha University Graduate School of Brain Science, Kyoto 610-0394, Japan. Electronic address: nnukina@mail.doshisha.ac.jp.
authors: Nobuyuki
authors: N
authors: Nukina
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism*; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D008817:Mice, Mutant Strains; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation; D011180:Postmortem Changes; D000071456:Sequestosome-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006360:Heat-Shock Proteins; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; C491079:Sqstm1 protein, rat
keywords: Alzheimer's disease; Amyotrophic lateral sclerosis; Dephosphorylation; Postmortem change; Protein degradation; Selective autophagy