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Application of brain-derived neurotrophic factor precursor protein as target for treating affective disorders

A technology of neurotrophic factors and precursor proteins, which can be used in anti-growth factor immunoglobulins, nervous system diseases, anti-animal/human immunoglobulins, etc., and can solve problems such as unclear role of proBDNF

Inactive Publication Date: 2017-03-01
周意
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is known in the prior art that neurotrophic factor precursors (including proNGF and proBDNF, etc.) can promote apoptosis and inflammatory responses, but the role of proBDNF in affective disorders is still unclear

Method used

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  • Application of brain-derived neurotrophic factor precursor protein as target for treating affective disorders
  • Application of brain-derived neurotrophic factor precursor protein as target for treating affective disorders
  • Application of brain-derived neurotrophic factor precursor protein as target for treating affective disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0232] Modeling and validation of depression in rats

[0233] According to the method described above, a rat model of depression was established by CUMS.

[0234] Compared with the control group, the results were statistically significant (p<0.05 or p<0.01) through OFT (including standing times, horizontal movement distance and immobility time), FST (immobility time) and SPT (sugar water consumption) behavioral tests ), confirmed the success of the depression rat model (Yang CR et al., 2014Neurotoxicity Research Neurotox Res.2014Apr; 25(3):235-47; Ruan CSet al., Eur J Neurosci.2014Aug; 40(4):2680 -90).

Embodiment 2

[0236] Protein and transcript level detection

[0237] 1. According to the above Western blot method, determine the rat Actin (actin, SEQ ID NO: 23), proBDNF (SEQ ID NO: 24), sortilin (SEQ ID NO: 26), p75 (SEQ ID NO: 25) and trkb (SEQ ID NO: 27) protein levels. The results are shown in Tables 11-17 below and Figure 11-14 .

[0238] Western blot results showed that the expression of proBDNF in the depression group was significantly higher than that in the control group in the hippocampus and cortex of rats (p<0.05).

[0239] Table 11: Comparison of proBDNF expression changes in cortex in rat depression model

[0240] group proBDNF / actin (%) control group 0.2754±0.027829(n＝3) depression group 0.3673±0.01582 * (n＝6)

[0241] * There is a difference between the depression group and the control group, p<0.05.

[0242] Table 12: Comparison of proBDNF expression changes in hippocampus in rat depression model ( N=5)

[0243] group proBDN...

Embodiment 3

[0330] Three factors of AAV8-BDNF, AAV8-proBDNF and AAV8-EGFP were injected intramuscularly

[0331] Injection method and dosage: Inject 50 μl of AAV8-BDNF, AAV8-proBDNF and AAV8-EGFP into the tibialis anterior muscle on both sides of the three groups of depression model mice (manufactured by Virovek according to the contract, see Yao et al., Mol Psychiatry., 2015PMID: 25917367) , diluted 1:1 with PBS and injected only once. Behavioral test evaluation was performed two weeks later.

[0332] After administering the above three factors, the results of immobility time, horizontal movement distance and sugar water consumption were detected by FST, OFT and SPT behavioral experiments respectively, see Table 6-10 and Figure 6-10 .

[0333] Table 6: After intramuscular injection of three factors, the comparison of the FST immobility time of three groups of rats ( N=7)

[0334] group Immobility time (s) AVV8-BDNF group 78.71±18.22 AVV8-proBDNF group 180.1±...

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Abstract

The invention belongs to the field of bio-pharmaceuticals, and in particular relates to an application of a binding molecule, which has a neutralizing or inhibiting activity on brain-derived neurotrophic factor precursor protein (proBDNF) or a signaling molecule thereof, or a binding molecule, which has a stimulating or promoting activity on the proBDNF or the signaling molecule thereof, in preparing medicines for preventing, relieving or treating affective disorders. The invention discovers that the proBDNF is an important target for treating the affective disorders including depression for the first time; and the binding molecule, which can specifically bind the proBDNF, can take an obvious effect of preventing, relieving or treating the affective disorders.

Description

technical field [0001] The invention belongs to the field of biopharmaceuticals, and in particular relates to the preparation of binding molecules with neutralizing or inhibitory activity to brain-derived neurotrophic factor precursor protein (proBDNF) or its signal transduction molecules for prevention, alleviation or treatment including depression Drug use in affective disorders. Background technique [0002] Depression is a mental disorder that seriously endangers human physical and mental health, and it seriously affects the daily work and life of patients. Statistics show that 15% of patients with depression are accompanied by suicidal tendencies, and nearly 60% of those who die by suicide suffer from depression or other types of emotional disorders. The World Health Report 2001 issued by the World Health Organization pointed out that depression has become the fourth largest disease in the world. It is projected that by 2020, depressive disorders will become one of th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P25/24A61P25/22
CPCA61K39/395C07K16/22C12N15/63
Inventor 周新富
Owner 周意