Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Application of HIF-1alpha micromolecular activator in preparation of medicine for treating neurodegenerative diseases

A neurodegenerative and drug technology, applied in the field of biomedicine, can solve problems such as the treatment effect of the neurodegenerative disease Parkinson's disease that has not yet been disclosed

Inactive Publication Date: 2019-03-01
SHANGHAI FIRST PEOPLES HOSPITAL
View PDF4 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, some preparation methods of this compound are mainly disclosed in the prior art, but its therapeutic effect in neurodegenerative diseases, especially Parkinson's disease, has not yet been disclosed

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
  • Application of HIF-1alpha micromolecular activator in preparation of medicine for treating neurodegenerative diseases
  • Application of HIF-1alpha micromolecular activator in preparation of medicine for treating neurodegenerative diseases
  • Application of HIF-1alpha micromolecular activator in preparation of medicine for treating neurodegenerative diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0173] Example 1: MPP + Inhibit SH-SY5Y cell proliferation, promote cell apoptosis, affect the expression of HIF-1α

[0174] In this example, use: MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model to evaluate SH-SY5Y cells (human neuroblastoma cells, widely used MPP in the study of the pathogenesis of PD + (methylphenylpyridinium ion) neurotoxicity.

[0175] We first used different concentrations (0, 1, 2, 3, 4, 5mM) of MPP + The cells were treated for 24 hours, and then the cell viability was detected by the CCK-8 method. We found that with a concentration of 3.5 mM MPP + Cell viability dropped to about 50% when treated ( figure 1 A), so we choose 3.5mM as the subsequent cell treatment concentration. Our results also show that the MPP + Increase the apoptosis of SH-SY5Y cells ( figure 1 B). Then we detected SH-SY5Y cells in different MPP + Concentration (0.3, 5.5mM) for 24 hours and 3.5mM for different time (0, 6, 12, 24, 36 hours) HIF-1α protein level. Suc...

Embodiment 2

[0176] Example 2: Compound FG-4592 increases HIF-1α expression and alleviates MPP in SH-SY5Y cells + induced cell damage

[0177] In this example, the effect of the compounds of the present invention on the accumulation of HIF-1α by inhibiting its degradation was tested.

[0178]Tyrosine hydroxylase (TH) is the rate-limiting enzyme for DA synthesis in dopaminergic (DA) neurons. The decrease of TH expression will lead to the decrease of dopamine secretion, leading to the clinical symptoms of Parkinson's disease. If TH expression increases after treatment, it indicates improvement in treatment. In addition, the existence of Lewy bodies containing α-synuclein (α-synuclein) aggregates in the substantia nigra is also the main pathological feature of PD. α-synuclein is the first PD-related gene discovered, and its mutant A53T (Ala53Thr), A30P (Ala30Pro) are the most common genotypes confirmed to be closely related to the pathogenesis of familial PD.

[0179] Our experiments foun...

Embodiment 3

[0183] Example 3: Mitochondrial function was significantly improved in dopaminergic neurons treated with compound FG-4592

[0184] In this example, the effect of compounds of the invention on mitochondrial oxygen consumption rate, maximal respiration and reserve respiratory capacity was tested.

[0185] Many studies have shown that mitochondrial dysfunction and oxidative stress may play a key role in the pathogenesis of PD. Dopaminergic neurons are susceptible to oxidative damage due to high levels of reactive oxygen species produced during DA synthesis or its breakdown by monoamine oxidase.

[0186] We measured FG-4592 (compound of formula Ia) and MPP + Mitochondrial membrane potential (MMP) in co-treated SH-SY5Y cells. It was shown that an increase in HIF-1α partially reversed the MPP + The reduction of cellular MMP caused by ( image 3 A, 3B) and reduction of ATP production ( image 3 C). In order to further explore the changes in the respiratory function of cells, we...

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 relates to the technical field of biological medicine, in particular to an application of an HIF-1alpha micromolecular activator in preparation of a medicine for treating neurodegenerative diseases, particularly PD (Parkinson's disease).

Description

[0001] This application requires Chinese Patent Application No. 201710713232.5 filed on August 18, 2017, entitled "Application of HIF-1α Small Molecule Activator FG-4592 in Parkinson's Disease" and filed on January 22, 2018, entitled The priority of Chinese patent application No. 201810058933.4 for "Application of small molecule activators of HIF-1α in the preparation of drugs for the treatment of neurodegenerative diseases". technical field [0002] The invention relates to the technical field of biomedicine, in particular to the application of a small molecule activator of HIF-1α in the treatment of neurodegenerative diseases, especially Parkinson's disease. Background technique [0003] Neurodegenerative diseases, also known as neurodegenerative diseases, usually manifest as progressive loss of structure or function of brain or nervous tissue. This is one of the major unsolved health problems in the world today. There are several types of neurodegenerative diseases. Tak...

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
Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/472A61P25/28A61P25/16A61P21/00
CPCA61P21/00A61P25/16A61P25/28A61K31/472
Inventor 吴云成尹慧勇李璇
Owner SHANGHAI FIRST PEOPLES HOSPITAL
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com