Abstract:
:Oxidative stress has been proposed as a potential mechanism for neurodegenerative diseases, such as Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS). In response to oxidative stress, the levels of numerous cytoprotective products are increased via alteration of the Kelch-like ECH-associated protein 1 (Keap1) and NF-E2-related factor 2 (Nrf2) system. One of the Nrf2 targets, p62, has been known to be incorporated into a wide spectrum of cytoplasmic inclusions in neurodegenerative diseases and interact with Keap1. However, it remains unclear whether Keap1 is associated with the pathogenesis of neurodegenerative diseases. In this study, we investigated the relationship between p62 and Keap1 in the brains of patients with AD, PD, dementia with Lewy bodies (DLB), and ALS. Biochemical analyses showed that p62 and Keap1 interacted with each other in AD and DLB brains and were extracted into similar detergent-soluble and -insoluble fractions. Pathologic examination demonstrated that anti-Keap1 antibodies immunostained Lewy bodies in PD and DLB, neurofibrillary tangles in AD, and skeinlike inclusions in ALS. Further analysis showed that the levels of common Nrf2 target genes were increased in AD compared with those in controls. However, there were no statistical significances in the levels of Nrf2 target genes in DLB relative to controls. Our pathologic and biochemical results suggest a molecular basis for stress response to be involved in the formation of cytoplasmic inclusions observed in several neurodegenerative diseases.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Tanji K,Maruyama A,Odagiri S,Mori F,Itoh K,Kakita A,Takahashi H,Wakabayashi Kdoi
10.1097/NEN.0b013e31827b5713subject
Has Abstractpub_date
2013-01-01 00:00:00pages
18-28issue
1eissn
0022-3069issn
1554-6578journal_volume
72pub_type
杂志文章abstract::Glial cytoplasmic inclusions (GCIs) are a pathologic hallmark of multiple system atrophy (MSA), but their pathogenetic roles need to be clarified. To determine possible roles of GCIs in individual cells, serial optical sections obtained by confocal microscopy were reconstructed to yield 3-dimensional (3D) images of th...
journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlaa077
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199809000-00008
更新日期:1998-09-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
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journal_title:Journal of neuropathology and experimental neurology
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doi:10.1093/jnen/60.9.839
更新日期:2001-09-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/60.5.449
更新日期:2001-05-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199708000-00008
更新日期:1997-08-01 00:00:00
abstract::Bergmann fibers and the distribution of Golgi epithelial cells were significantly altered in staggerer, reeler and double mutant (affected by both staggerer and reeler conditions). However, the Bergmann fiber anomalies in double mutant were not identical to those of either staggerer or reeler. A comparison of these an...
journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/00005072-197705000-00003
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abstract::In the present study, we investigated the expression of protease-activated receptors (PARs), receptors for thrombin, in substantia nigra pars compacta (SNpc) of Parkinson disease (PD) brains and cultures of human neurons, astrocytes, oligodendrocytes, and microglia as determined by immunocytochemistry and reverse tran...
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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更新日期:2002-06-01 00:00:00
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199411000-00006
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
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