Abstract:
:The normal cellular isoform of prion protein, designated PrPC, is constitutively converted to the abnormally folded, amyloidogenic isoform, PrPSc, in prion diseases, which include Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. PrPC is a membrane glycoprotein consisting of the non-structural N-terminal domain and the globular C-terminal domain. During conversion of PrPC to PrPSc, its 2/3 C-terminal region undergoes marked structural changes, forming a protease-resistant structure. In contrast, the N-terminal region remains protease-sensitive in PrPSc. Reverse genetic studies using reconstituted PrPC-knockout mice with various mutant PrP molecules have revealed that the N-terminal domain has an important role in the normal function of PrPC and the conversion of PrPC to PrPSc. The N-terminal domain includes various characteristic regions, such as the positively charged residue-rich polybasic region, the octapeptide repeat (OR) region consisting of five repeats of an octapeptide sequence, and the post-OR region with another positively charged residue-rich polybasic region followed by a stretch of hydrophobic residues. We discuss the normal functions of PrPC, the conversion of PrPC to PrPSc, and the neurotoxicity of PrPSc by focusing on the roles of the N-terminal regions in these topics.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Hara H,Sakaguchi Sdoi
10.3390/ijms21176233subject
Has Abstractpub_date
2020-08-28 00:00:00issue
17issn
1422-0067pii
ijms21176233journal_volume
21pub_type
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
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journal_title:International journal of molecular sciences
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更新日期:2017-11-13 00:00:00
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journal_title:International journal of molecular sciences
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更新日期:2019-10-24 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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更新日期:2017-08-22 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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更新日期:2019-10-13 00:00:00
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journal_title:International journal of molecular sciences
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更新日期:2020-03-20 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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更新日期:2020-05-26 00:00:00
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journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21051758
更新日期:2020-03-04 00:00:00
abstract::Kaempferol (Kae), a natural flavonoid, is widely distributed in fruits and vegetables. Previous studies have identified Kae as a possible cancer preventive and therapeutic agent. We found Kae to exhibit potent antiproliferation and anti-migration effects in human bladder cancer EJ cells. Kaempferol robustly induced ap...
journal_title:International journal of molecular sciences
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doi:10.3390/ijms141121215
更新日期:2013-10-24 00:00:00