Applications of small-molecule activating agent and antagonist of serotonin receptor subtype 6 in preventing and treating alzheimer disease

A technology of serotonin receptors and antagonists, applied in the field of life science research, can solve the problems of low homology of HTR sequences and affecting the process of AD, etc.

Inactive Publication Date: 2018-12-04
CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
View PDF7 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] 3) Anti-inflammatory treatment, the anti-AD effect of non-steroidal anti-inflammatory drugs may affect the process of AD by inhibiting the abnormal proliferation of microglial cells
[0009] 5) Drugs that interfere with β-amyloid deposition, etc. Since the etiological mechanis

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Applications of small-molecule activating agent and antagonist of serotonin receptor subtype 6 in preventing and treating alzheimer disease
  • Applications of small-molecule activating agent and antagonist of serotonin receptor subtype 6 in preventing and treating alzheimer disease
  • Applications of small-molecule activating agent and antagonist of serotonin receptor subtype 6 in preventing and treating alzheimer disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Embodiment 1 QPCR detects the background expression level of serotonin receptor in the target cell line

[0086] SK-N-SH is a neuroblastoma cell line with constitutive low-level Aβ production. In order to confirm whether it is suitable for related research in this cell line, we firstly measured the background expression level of serotonin receptors in cells by QPCR. Tested. Such as figure 1 As shown, it was found that serotonin receptor subtype 6 was expressed at a higher level on the SK-N-SH cell line.

Embodiment 2 5

[0087] Example 2 Antagonists of serotonin receptor subtype 6 can reduce Aβ production in a dose-dependent manner

[0088] Using Aβ production experiments, we found that if figure 2 As shown, SB258585hydrochloride, an antagonist targeting serotonin receptor subtype 6, decreased Aβ production in a dose-dependent manner.

Embodiment 3

[0089] Example 3 The effect of SB258585hydrochloride on reducing Aβ production is dependent on serotonin receptor subtype 6

[0090] In order to investigate whether the effect of SB258585hydrochloride on reducing Aβ production is dependent on serotonin receptor subtype 6, we performed shRNA-mediated knockdown of serotonin receptor subtype 6 expression by lentivirus. Scrambled with random nucleotide sequence was expressed as a negative control, and the knockdown efficiency of shRNA-mediated serotonin receptor subtype 6 expression was detected by fluorescent real-time quantitative PCR. Such as image 3 As shown, the experimental results of fluorescent real-time quantitative PCR show that the viral transfection targeting serotonin receptor subtype 6 shRNA can cause its mRNA level to decrease by about 60%. Compared with the control group, after transfection of shRNA targeting the serotonin receptor HTR6 sequence, antagonist stimulation can still reduce Aβ production in the contro...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention belongs to the field of life science research, and in particular relates to applications of an antagonist of serotonin receptor subtype 6 in preparing amyloid protein beta-amyloid inhibitors. According to the applications, for the first time, the elisa experiment is adopted for proving that an activating agent and the antagonist targeting to the serotonin receptor subtype 6 can reduce the generation of the amyloid protein beta-amyloid on the human nerve cell line, in the cerebrospinal fluid of patients, the concentration change of beta-amyloid is earlier than the change of the tau protein level, the deposition of amyloid protein is also earlier than the occurrence of the clinical symptoms, and considering that the process from the accumulation of beta-amyloid small peptide tothe plaque formation depends on the concentration of beta-amyloid, the searching for the method for reducing the concentration of beta-amyloid is very important for treatment. Therefore, the disclosure for the fact that the activating agent and the antagonist targeting to the serotonin receptor subtype 6 can reduce the generation of beta-amyloid and for the related mechanism can provide the guiding significance of the clinical experiment for the treatment of the alzheimer disease and the further research and development of medicines.

Description

technical field [0001] The invention belongs to the field of life science research, and in particular relates to the use of an antagonist of serotonin receptor subtype 6 (HTR6) in the preparation of an amyloid (Aβ) inhibitor. Background technique [0002] Alzheimer's disease (AD), also known as senile dementia, is a degenerative disease of the central nervous system with insidious onset and slow progressive course, and is the most common type of senile dementia. According to the different origins in the population, AD can be divided into two types: sporadic and familial, of which about 5% are familial cases. Studies on such cases have shown that mutations in APP, PSEN1 and PSEN2 genes are associated with AD The pathogenesis of most other sporadic cases is not clear. According to the development of the disease, it can be divided into four stages. The first stage is often wrongly attributed to aging or stress, and it is generally some distance away from the exact pathological ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K31/495A61K31/496A61K31/4045A61K45/00A61P25/28
CPCA61K45/00A61K31/4045A61K31/495A61K31/496
Inventor 裴钢李晓行王勤英陆婧
Owner CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products