Abstract:
:Alzheimer's disease is believed to begin with synaptic dysfunction caused by soluble Aβ oligomers. When this oligomer hypothesis was proposed in 2002, there was no direct evidence that Aβ oligomers actually disrupt synaptic function to cause cognitive impairment in humans. In patient brains, both soluble and insoluble Aβ species always coexist, and therefore it is difficult to determine which pathologies are caused by Aβ oligomers and which are caused by amyloid fibrils. Thus, no validity of the oligomer hypothesis was available until the Osaka mutation was discovered. This mutation, which was found in a Japanese pedigree of familial Alzheimer's disease, is the deletion of codon 693 of APP gene, resulting in mutant Aβ lacking the 22nd glutamate. Only homozygous carriers suffer from dementia. In vitro studies revealed that this mutation has a very unique character that accelerates Aβ oligomerization but does not form amyloid fibrils. Model mice expressing this mutation demonstrated that all pathologies of Alzheimer's disease can be induced by Aβ oligomers alone. In this review, we describe the story behind the discovery of the Osaka mutation, summarize the mutant's phenotypes, and propose a mechanism of its recessive inheritance.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Tomiyama T,Shimada Hdoi
10.3390/ijms21041413subject
Has Abstractpub_date
2020-02-19 00:00:00issue
4issn
1422-0067pii
ijms21041413journal_volume
21pub_type
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journal_title:International journal of molecular sciences
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doi:10.3390/ijms21186460
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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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journal_title:International journal of molecular sciences
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更新日期:2020-07-31 00:00:00
abstract::Interferon (IFN)-γ is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-γ is well known regarding its inhibitory effects on collagen synthesis by fibroblasts in vitro, information is limited regarding its role in wound healing in vivo. In the present study, we ...
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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:2017-05-03 00:00:00
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journal_title:International journal of molecular sciences
pub_type: 社论
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journal_title:International journal of molecular sciences
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更新日期:2019-05-11 00:00:00
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journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
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更新日期:2019-09-27 00:00:00
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journal_title:International journal of molecular sciences
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