Autophagy-related proteins (p62, NBR1 and LC3) in intranuclear inclusions in neurodegenerative diseases.
Incorporation of ubiquitin and ubiquitin-related proteins including p62 into neuronal intranuclear inclusions (NIIs) has been reported in a variety of neurodegenerative diseases. However, involvement of autophagy-specific proteins (NBR1 and LC3) in NIIs has not been mentioned. We immunohistochemically examined the brain of patients with Machado-Joseph disease (MJD; n=5), dentatorubral-pallidoluysian atrophy (DRPLA; n=5) and intranuclear inclusion body disease (INIBD; n=5), using antibodies against ubiquitin, p62, NBR1 and LC3. The proportion of p62-, NBR1- and LC3-positive inclusions relative to the number of ubiquitin-positive inclusions was calculated in each case. NIIs were positive for p62 in MJD (19.3%), DRPLA (49.7%) and INIBD (99.8%). As for autophagy-specific proteins, NIIs were positive for NBR1 in MJD (4.2%), DRPLA (5.5%) and INIBD (13.2%) and negative for LC3 in MJD, DRPLA and INIBD, except for one case of INIBD. These findings suggest that autophagy-lysosome pathway is not involved in the formation/degradation of NIIs.
Department of Neuropathology, Cell Biology and Histology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. neuropal@cc.hirosaki-u.ac.jp
Fumiaki
F
Mori
Kunikazu
K
Tanji
Saori
S
Odagiri
Yasuko
Y
Toyoshima
Mari
M
Yoshida
Akiyoshi
A
Kakita
Hitoshi
H
Takahashi
Koichi
K
Wakabayashi
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001343:Autophagy; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D000071456:Sequestosome-1 Protein
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C549756:NBR1 protein, human; D011506:Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein