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Novel mutation of Alzheimer disease, stable transfer cell model and medical application thereof

An Alzheimer's disease, cell technology, applied in the field of biomedicine, can solve problems such as neurotoxicity, weakened carboxypeptidase activity, and increased Aβ peptide production

Active Publication Date: 2019-05-21
XUANWU HOSPITAL OF CAPITAL UNIV OF MEDICAL SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

PSEN1 mutation weakens the carboxypeptidase activity of γ-secretase, leading to a relative increase in the production of longer Aβ peptides, which are more hydrophobic, more prone to self-aggregation, and more neurotoxic, which in turn causes Aβ deposition and other signs of AD Sexual pathological changes, leading to the onset of AD

Method used

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  • Novel mutation of Alzheimer disease, stable transfer cell model and medical application thereof
  • Novel mutation of Alzheimer disease, stable transfer cell model and medical application thereof
  • Novel mutation of Alzheimer disease, stable transfer cell model and medical application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0125] Example 1: Screening and sequencing of Alzheimer's disease-causing genes

[0126] 1. Experimental method

[0127] Family collection and genetic testing: Collect clinical data and blood samples from two AD families in the China Familial Alzheimer's Disease Registration Network (CFAN, www.chinacfan.org), screen PSEN1, PSEN2, APP gene mutations and detect APOE genotype. Written informed consent has been obtained.

[0128] 2. Experimental results

[0129] The PSEN1 mutation was found, that is, the two families carried PSEN1I249L and P433S new mutations respectively, and the family diagrams are as follows Figure 1A ,and Figure 1B As shown, the sequencing results are as follows Figure 1C and Figure 1D shown.

[0130] The proband of the I249L mutation family was a 58-year-old housewife who had progressive memory loss for 4 years. She developed personality changes and social withdrawal within 1 year of onset, and her condition gradually worsened. Disorientation and ...

Embodiment 2

[0135] Embodiment 2: cytology experiment

[0136] 1. Experimental method

[0137] (1) Construction of lentiviral expression vector, site-directed mutagenesis and identification

[0138] The pcDNA3.1-wtPSEN1-EGFP plasmid comes from the previous work of our laboratory (Fang Boyan. Study on Pathological Function of Presenilin 1 Gene Mutation in Chinese Familial Alzheimer's Disease [Ph.D.]: Capital Medical University; 2006.). The lentiviral expression vector pLVX-IRES-ZsGreen1 (Clontech, Catalog No.632187), the lentiviral packaging plasmid pSPAX2 (Addgene, Catalog No.12260) and the envelope plasmid pMD2G (Addgene, Catalog No.12259) were provided by Professor Li Hongzhi of Wenzhou Medical University gift 14 .

[0139] Using the pcDNA3.1-wtPSEN1-EGFP plasmid (other plasmids inserted with PSEN1 can also be used), amplify and purify the PCR product by PCR, and recover the target fragment PSEN1. The target fragment PSEN1 can also be prepared by other means known to those skilled ...

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Abstract

The invention belongs to the field of biological medicine, and relates to mutein of Alzheimer disease, a mutant gene and a medical application thereof. Particularly, the invention relates to two novelmutation sites of presenilin 1 encoded by familial Alzheimer disease pathogenic gene PSEN1. More specifically, the invention relates to protein with an amino acid sequence shown in any one of SEQ IDNOs: 1-2. The inventor finds the two novel mutations of the PSENN 1, which are closely related to the onset of various families of AD, have the potential to be used in the preparation of a medicamentor agent for the treatment and / or prevention or diagnosis of Alzheimer disease.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a new mutation of Alzheimer's disease, its stably transformed cell model and its medical application. Specifically, the present invention relates to two new mutation sites of presenilin 1 (presenilin 1) encoded by the familial Alzheimer's disease-causing gene PSEN1. Background technique [0002] Alzheimer's disease (AD) is the most common type of dementia, and its three major disease genes PSEN1 1 、APP 2 and PSEN2 3,4 The mutation of Aβ and its clinical cases, as well as biochemical and animal model studies point to the pathogenic effect of Aβ on AD. The reports of its family and the exploration of mutations will help to further reveal the pathogenesis of AD. [0003] Aβ is produced by APP processing. There are two competing pathways for APP processing 5 : One way is not to generate Aβ, that is, it is first cleaved by α-secretase to generate sAPPα and αAPP-CTF (C83), and then C83 is...

Claims

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Application Information

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IPC IPC(8): C07K14/47C12N15/12C12N15/85C12N5/10C12N15/11C07K16/18G01N33/68C12Q1/6883A61K39/395A61P25/28A61K49/00
Inventor 贾建平沈露茜
Owner XUANWU HOSPITAL OF CAPITAL UNIV OF MEDICAL SCI
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