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Novel application of aromatic cyclopropyl amine compound

A technology of cyclopropylamine and compounds, which is applied in the field of aromatic cyclopropylamine compounds, can solve the problems of unknown protective effect on nerve cells

Active Publication Date: 2017-10-31
EYE & ENT HOSPITAL SHANGHAI MEDICAL SCHOOL FUDAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] However, the protective effect of aromatic cyclopropylamines on nerve cells in peripheral neuropathy is still unknown

Method used

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  • Novel application of aromatic cyclopropyl amine compound
  • Novel application of aromatic cyclopropyl amine compound
  • Novel application of aromatic cyclopropyl amine compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] Establishment of mouse cochlear spiral neuron injury model in vitro. The spiral neuron tissue of the cochlea in the middle circle was selected, injured with gentamicin for 48 hours, and then eluted for 12 hours, and the loss of nerve cells could be detected in the spiral neurons cultured in vitro. The present invention selects the gentamicin injury model to further study the injury and protection of spiral neurons.

[0096] Firstly, the cochlear auditory epithelium of newborn mice was separated, and the middle circle of the tissue was carefully cut out, and adhered to the wall for 4 hours. After the specimen adhered to the wall, it was added to the experimental group (compound A, B, C, D, E, F, G or H treatment group ) or the serum-free DMEM / F12 culture medium of control group drug co-cultured for 24 hours, then added the serum-free DMEM / F12 culture medium containing 1mM gentamycin and co-cultured for 48 hours. Finally, serum-free medium was added for co-cultivation fo...

Embodiment 2

[0099] Dimethylated histone H3K4 expression level detection. Follow the in vitro culture protocol for mouse cochlear spiral neuron culture. Take the control group, compound A, B, C, D, E, F, G or H treatment group to treat cochlear spiral neurons, and treat them with gentamicin injury for 24 hours, and use immunofluorescence staining to detect the expression level of histones, And Western blot was used for semi-quantitative detection. Wherein, compared with the control group, the treatment situation of Compound A and Compound B treatment groups is shown in Figure 2A , 2B , 2C.

[0100] Depend on Figure 2A , 2B , 2C, it can be seen that the histone H3K4me2 in the spiral neurons of the normal group has a certain intensity expression, and the expression intensity of H3K4me2 in the spiral neurons after gentamicin injury is significantly down-regulated. In order to semi-quantitatively verify the effect of gentamicin injury on the expression of H3K4me2, the results of Wester...

Embodiment 3

[0103]Spiral neuron apoptosis assay. According to the in vitro culture protocol, the mouse cochlear spiral neurons were cultured, and the injury group, the compound A, B, C, D, E, F, G or H treatment group were respectively taken to treat the cochlear basement membrane or spiral neurons, and the gentamicin-injured After 24 hours, the expression level of Cleaved Caspase-3 was detected semi-quantitatively by Western blot.

[0104] The specific steps are as follows (Western blot quantitative detection of Cleaved Caspase-3 expression): ( Figure 3A , 3B );

[0105] ① Total protein extraction (AllPrep DNA / RNA / Protein Mini Kit, QIAGEN, Hilden, Germany)

[0106] a. For each group of 12 basement membrane or 12 spiral neuron tissues, the tissue was thoroughly ground on ice with an ultrasonic homogenizer (350 μl RLT + 3.5 μl β-mercaptoethanol), 4° C., 1200 rpm, and centrifuged for 3 minutes.

[0107] b. Add the supernatant to the Allprep DNA spin column collection tube (purple colum...

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Abstract

The invention belongs to the technical field of biology, relates to a novel application of an aromatic cyclopropyl amine compound and provides an application of an aromatic cyclopropyl amine compound, which is used for preparing drugs for preventing and treating peripheral neuropathy as an effective ingredient. An animal model for in vitro injury and protection study of a spiral ganglion neuron is built by taking injury protection of the spiral ganglion neuron in sensorineural deafness as an example and a mouse as a model animal, and the result shows that the dimethylated histone H3K4 expression level can be obviously regulated up and Cleaved Caspase-3 expression of the spiral ganglion neuron can be significantly reduced through providing the aromatic cyclopropyl amine compound in vitro, and the aromatic cyclopropyl amine compound has a protective effect on peripheral nerve cells, especially the spiral ganglion neuron of a sensorineural deafness patient. A theoretical basis and a new way are provided for searching, preventing and treating the peripheral neuropathy, and the aromatic cyclopropyl amine compound has clinical application value.

Description

technical field [0001] The invention belongs to the field of biotechnology, and relates to a new use of aromatic cyclopropylamine compounds, in particular to the use of aromatic cyclopropylamine compounds in the preparation of medicines for preventing and / or treating peripheral neuropathy. Background technique [0002] Peripheral nerves can be divided into cranial nerves connected to the brain and spinal nerves connected to the spinal cord according to the different parts connected to the central nervous system. Damage and destruction of peripheral nerves can lead to a variety of diseases, collectively known as peripheral neuropathy. There are many kinds of cranial nerve diseases, among which the common ones include: trigeminal neuralgia, idiopathic facial paralysis, hemifacial spasm, multiple cranial nerve damage, sensorineural deafness, etc.; and common spinal nerve diseases include: mononeuropathy and neuropathy pain, polyneuropathy, acute inflammatory demyelinating poly...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/137A61P25/02A61P25/28A61P25/00A61P29/00A61P27/16
CPCA61K31/137
Inventor 黎奥李华伟何英姿唐冬梅于慧前柴人杰崔英杰孔令富冯虓
Owner EYE & ENT HOSPITAL SHANGHAI MEDICAL SCHOOL FUDAN UNIV
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