Abstract:
:Niemann-Pick disease type C (NP-C) is an autosomal recessive neurovisceral storage disease with neurodegeneration caused by mutations in either the NPC-1 or NPC-2 gene. The murine ortholog of NPC-1 is mutated in BALB/c npc(nih) and this mutant mouse shows equally conspicuous neurodegeneration and loss of neurons. However, the molecular mechanisms causing neurodegeneration in NP-C remain elusive. Here, we report the presence of apoptotic cells detected by both TUNEL staining and electron microscopy in the cerebrum and cerebellum of human patients and the mouse model. Moreover, we found that with progression of the disease process leading to neuronal cell death, an up-regulation of genes involved in the TNF-alpha death pathway caspase-8, FADD, TNFRp55, TRADD, and RIP-by an RNA protection assay. Furthermore, RT-PCR showed that TNF-alpha mRNA expression level also increased up to 30-50-fold in the cerebellum of 7- and 9-week-old NP-C mice compared with wild-type mice. Elevated expression of TNF-alpha was detected in both neurons and astrocytes with TNF-alpha-expressing astrocytes distributed in the affected brain regions. Collectively, our results suggest that the cell death in the brain of NP-C disease occurs through apoptosis and it is mediated by the TNF receptor superfamily pathway.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Wu YP,Mizukami H,Matsuda J,Saito Y,Proia RL,Suzuki Kdoi
10.1016/j.ymgme.2004.08.017subject
Has Abstractpub_date
2005-01-01 00:00:00pages
9-17issue
1eissn
1096-7192issn
1096-7206pii
S1096-7192(04)00218-5journal_volume
84pub_type
杂志文章abstract::Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase gene (PAH), while mutations in genes encoding the two enzymes (dihydropteridine reductase, DHPR, and pterin-4-alpha-carbinolamine dehydratase, PCD) required for recycling of its cofactor, tetrahydrobiopterin (BH(4)), cause other rarer diseas...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2010-12-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2004.01.010
更新日期:2004-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1006/mgme.2001.3260
更新日期:2001-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2013-01-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1006/mgme.2000.3071
更新日期:2000-09-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2013.06.007
更新日期:2013-09-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2004.07.009
更新日期:2004-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s1096-7192(02)00037-9
更新日期:2002-07-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2010-06-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.06.016
更新日期:2010-10-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 临床试验,杂志文章
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更新日期:2004-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2008.01.015
更新日期:2008-06-01 00:00:00
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pub_type: 杂志文章,meta分析
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更新日期:2011-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2007-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2011-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.10.006
更新日期:2012-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2021-01-14 00:00:00
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pub_type: 杂志文章
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更新日期:2012-09-01 00:00:00