Serine 403-phosphorylated p62/SQSTM1 immunoreactivity in inclusions of neurodegenerative diseases

被引:17
作者
Kurosawa, Masaru [2 ,3 ,7 ,8 ]
Matsumoto, Gen [1 ,2 ,3 ,8 ]
Sumikura, Hiroyuki [4 ,5 ]
Hatsuta, Hiroyuki [4 ,5 ]
Murayama, Shigeo [4 ,5 ]
Sakurai, Takashi [7 ]
Shimogori, Tomomi [3 ]
Hattori, Nobutaka [6 ]
Nukina, Nobuyuki [1 ,2 ,3 ,8 ,9 ]
机构
[1] Juntendo Univ, Grad Sch Med, Dept Neurosci Neurodegenerat Disorders, Tokyo 1138421, Japan
[2] RIKEN Brain Sci Inst, Lab Struct Neuropathol, Wako, Saitama 3510198, Japan
[3] RIKEN Brain Sci Inst, Lab Mol Mech Thalamus Dev, Wako, Saitama 3510198, Japan
[4] Tokyo Metropolitan Geriatr Hosp, Dept Neurol & Neuropathol, Tokyo 1730015, Japan
[5] Inst Gerontol, Tokyo 1730015, Japan
[6] Juntendo Univ, Grad Sch Med, Dept Neurol, Tokyo 1138421, Japan
[7] Juntendo Univ, Grad Sch Med, Dept Cellular & Mol Pharmacol, Tokyo 1138421, Japan
[8] JST, CREST, Tokyo 1020076, Japan
[9] Doshisha Univ, Grad Sch Brain Sci, Lab Struct Neuropathol, Kyoto 6100394, Japan
关键词
Selective autophagy; Alzheimer's disease; Amyotrophic lateral sclerosis; Postmortem change; Dephosphorylation; Protein degradation; AMYOTROPHIC-LATERAL-SCLEROSIS; SELECTIVE AUTOPHAGY; ALZHEIMERS-DISEASE; TRANSGENIC MICE; BINDING PROTEIN; P62; CELLS; PHOSPHORYLATION; EXPRESSION; NEURONS;
D O I
10.1016/j.neures.2015.08.002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
引用
收藏
页码:64 / 70
页数:7
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