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Use of p75neurotrophin receptor-extracellular domain (p75NTR-ECD) in medicine for preventing and treating Alzheimer disease

A technology of Alzheimer's disease and p75ntr-ecd, which is applied in the field of biomedicine to achieve the effect of broad clinical application prospects

Active Publication Date: 2011-11-09
SUZHOU AUZONE BIOLOGICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

During the metabolic process, p75NTR is cleaved by enzymes to release its extracellular segment (hereinafter referred to as p75NTR-ECD). The role of this extracellular segment in the pathogenesis of Alzheimer's disease has not been reported so far

Method used

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  • Use of p75neurotrophin receptor-extracellular domain (p75NTR-ECD) in medicine for preventing and treating Alzheimer disease
  • Use of p75neurotrophin receptor-extracellular domain (p75NTR-ECD) in medicine for preventing and treating Alzheimer disease
  • Use of p75neurotrophin receptor-extracellular domain (p75NTR-ECD) in medicine for preventing and treating Alzheimer disease

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0047] Experimental example 1: p75NTR-ECD and p75NTR-ECD / Fc inhibit Aβ42 oligomer formation

[0048] Mix 2.5 μg Aβ42 (final concentration 20 mM) with p75NTR-ECD / Fc (final concentration 10 mM), p75NTR-ECD (final concentration 10 mM) or human IgG (hereinafter referred to as HuIgG, final concentration 10 mM), 4 oC for 1 day. The same amount of Aβ42 (final concentration: 20 mM) was not incubated, or the same amount of Aβ42 (final concentration: 20 mM) was incubated alone at 4 oC as a control. Then perform protein electrophoresis, and use 6E10-biotin antibody for western blot detection to determine the content of Aβ42 oligomer bands.

[0049] Such as figure 1 As shown, compared with the Aβ42 single incubation group (Ab) (for the convenience of comparison, the Aβ42 oligomer content of this group is taken as 100%), the Aβ42 oligomer content of the HuIgG and Aβ42 co-incubation group (Ab+HuIgG) was 78 %, Aβ42 oligomer content of Aβ42 and p75NTR-ECD co-incubation group (Ab+p75NTR-EC...

experiment example 2

[0050] Experimental example 2: p75NTR-ECD and p75NTR-ECD / Fc inhibit Aβ42 fibril formation

[0051] Mix 2.5 μg Aβ42 (final concentration 20 mM) with p75NTR-ECD / Fc (final concentration 10 mM), p75NTR-ECD (final concentration 10 mM) or HuIgG (final concentration 10 mM), and incubate at 37 oC for 4 days. The same amount of Aβ42 (final concentration of 20 mM) was not incubated, or the same amount of Aβ42 (final concentration of 20 mM) was incubated alone at 37 oC as a control. Then add Thioflavine T to detect the fluorescence intensity (excitation wavelength 450nm, emission wavelength 482nm). The higher the fluorescence intensity, the more Aβ fibers.

[0052] Such as figure 2 As shown, compared with the Aβ single incubation group (Ab) (for convenience of comparison, the fluorescence intensity of this group is taken as 100%), the fluorescence intensity of the HuIgG and Aβ co-incubation group (Ab+HuIgG) is 103%, and the Aβ42 and p75NTR-ECD The fluorescence intensity of co-incubat...

experiment example 3

[0053] Experimental example 3: p75NTR-ECD and p75NTR-ECD / Fc promote the depolymerization of Aβ42 fibers

[0054] Firstly, 2.5 μg Aβ42 was dissolved in DMEM (final concentration 20 mM) and incubated at 37 oC for 4 days to form Aβ42 fibers. The formed Aβ42 fibers were mixed with p75NTR-ECD (final concentration 10 μM), p75NTR-ECD / Fc (final concentration 10 μM) or HuIgG (final concentration 10 μM), and incubated at 37 oC for 3 days. Then add Thioflavine T to detect the fluorescence intensity (excitation wavelength 450nm, emission wavelength 482nm). The higher the fluorescence intensity, the more Aβ fibers.

[0055] Such as image 3 As shown, the results show that compared with the Aβ fiber incubation group (Ab) alone (for convenience of comparison, this group of fluorescence is taken as 100%), the fluorescence intensity of the Aβ fiber co-incubation group with p75NTR-ECD (Ab+p75NTR-ECD) is 56 %, the fluorescence intensity of Aβ fibers incubated with p75NTR-ECD / Fc group (Ab+p75N...

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Abstract

The invention discloses a medicine for preventing and treating Alzheimer disease. The medicine may comprise p75NTR-ECD of which the nucleotide sequence is represented by the nucleotide sequence SEQ ID No.1 in a sequence table and of which the amino acid sequence is represented by amino acid sequence SEQ ID No.2 in the sequence table. The medicine also may be p75NTR-ECD / Fc of which the nucleotide sequence is represented by the nucleotide sequence SEQ ID No.3 in the sequence table and of which the amino acid sequence is represented by amino acid sequence SEQ ID No.4 in the sequence table. The medicine has the effects of inhibiting Abeta from aggregating into oligomer and fiber, promoting the depolymerization of Abeta fibers, eliminating Abeta in head and resisting Abeta neurotoxicity. The invention provides the new medicine for treating Alzheimer disease, which has a plurality of effects and has a bright clinic application prospect.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a medicine for preventing and treating Alzheimer's disease. Background technique [0002] The English word for Alzheimer's disease is Alzheimer's disease, usually abbreviated as AD. Dementia is a progressive neurodegenerative disease characterized by dementia, and it is an important disease that endangers the health and life of the elderly. At present, there are about 26 million AD patients in the world, and 5 million new cases are diagnosed every year. It is estimated that there will be more than 100 million AD patients in the world by 2040-2050. AD has become the main cause of death in the current population, and the 4th to 5th cause of death in people over 65 years old. The economic burden brought by AD to the family and society ranks third among all diseases, second only to heart disease and cancer. China is facing a severe situation of population aging and is the country with t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K39/395C12N15/62A61P25/28
Inventor 王延江周新富
Owner SUZHOU AUZONE BIOLOGICAL TECH CO LTD
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