CN-122005759-A - Application of activin A in preparation of nerve regeneration medicine

Abstract

The invention discloses an application of activin A in preparation of a nerve regeneration medicament. The invention provides and verifies that the activin A can promote the repair and regeneration of nerve injury through the synergic regulation and control of schwann cells and neurons for the first time, and provides a new direction for the treatment of diseases caused by nerve injury.

Inventors

• YI CHENG
• DAI WENYU
• SHEN YINYING
• YANG ZIHAN

Assignees

• 南通大学

Dates

Publication Date

20260512

Application Date

20260325

Claims (10)

1. 1. An application of activin A in preparing nerve regeneration medicine is disclosed.
2. 2. The use according to claim 1, wherein the use is in the manufacture of a medicament for the treatment of a disease caused by nerve damage.
3. 3. The use according to claim 2, wherein the disease caused by nerve damage comprises a disease caused by physical and/or physiological damage of the nerve of the disease caused by physical and/or physiological damage of the peripheral nerve.
4. 4. The use according to any one of claims 1 to 3, wherein the medicament comprises activin a recombinant protein or a derivative thereof as an active ingredient.
5. 5. The use according to claim 4, wherein the derivative comprises a protein modified at the pharmaceutically acceptable C-and/or N-terminus and/or side chain and/or intermediate residues of an activin a recombinant protein, or a salt, solvate, hydrate of an activin a recombinant protein.
6. 6. The use according to claim 5, wherein the modification of the C-terminal and/or N-terminal and/or side chain and/or intermediate residues is any one or more of acylation, amidation, alkylation, esterfication, glycosylation, phosphorylation.
7. 7. The use according to any one of claims 1 to 3, wherein the medicament comprises an activin a expression enhancer as an active ingredient.
8. 8. The use according to claim 7, wherein the enhancer of activin a expression is an overexpression vector comprising an expression cassette for an activin a encoding gene.
9. 9. The use according to claim 8, wherein the over-expression vector is a viral vector or a non-viral vector.
10. 10. The use according to claim 1, wherein the pharmaceutical dosage form comprises a tablet, capsule, granule, sustained release tablet, pellet, injection, infusion solution, suspension, patch, suppository, transdermal patch, microemulsion liposome, nanoparticle.

Description

Application of activin A in preparation of nerve regeneration medicine Technical Field The invention relates to the field of biological medicine, in particular to application of activin A in preparation of a nerve regeneration medicine. Background Peripheral nerve injury is a clinical common disabling disease, is often caused by factors such as wound, traction or compression, and can lead to permanent motor, sensory and autonomic nerve dysfunction, and seriously affects the life quality of patients. Although the peripheral nervous system has some regenerative capacity compared to the central nervous system, functional recovery is still far from satisfactory clinically for patients with large neurological defects, chronic injuries or complications. Failure of regenerative repair after injury is centered on limited schwann cell function that constitutes myelin sheath. After injury occurs, schwann cells undergo reprogramming similar to epithelial-to-mesenchymal transition, transforming into a repair phenotype, building a supportive microenvironment for axon regeneration. In this complex regulatory network, transforming growth factor-beta signaling pathways are key regulatory hubs. As an important member of TGF- β superfamily, activin a (Activin a) has been found to be significantly upregulated in expression following nerve injury and promote proliferation and migration of schwann cells. However, it is not clear whether Activin a can contribute further to nerve injury regeneration. Disclosure of Invention The invention aims to provide an application of activin A in preparing a nerve regeneration medicament by synergic regulation and control of schwann cells and neurons. The technical scheme is that the activin A is applied to the preparation of the nerve regeneration medicine. Preferably, the amino acid sequence of the activin A in rats is shown as UniProtKB_P18331, and the coding gene sequence of the activin A is shown as NCBI Reference Sequence:NM_ 017128.2. Preferably, the application is the application in preparing a medicament for treating diseases caused by nerve injury. Preferably, the disease caused by nerve injury comprises a disease caused by physical and/or physiological injury of peripheral nerve. Preferably, the medicament takes the activin A recombinant protein or a derivative thereof as an active ingredient, further preferably, the derivative comprises a protein modified by the activin A recombinant protein at a pharmaceutically acceptable C-terminal end and/or N-terminal end and/or side chain and/or intermediate residue, or a salt, a solvate and a hydrate of the activin A recombinant protein, further preferably, the modification of the C-terminal end and/or N-terminal end and/or side chain and/or intermediate residue is any one or more of acylation, amidation, alkylation, esterification, glycosylation and phosphorylation. Preferably, the medicament takes an activin A expression enhancer as an active ingredient, further preferably, the activin A expression enhancer is an over-expression vector containing an activin A coding gene expression cassette, and further preferably, the over-expression vector is a viral vector or a non-viral vector. Preferably, the dosage forms of the medicine comprise tablets, capsules, granules, sustained release tablets, micropills, injection, infusion solution, suspension, patches, suppositories, transdermal patches, microemulsion liposomes and nanoparticles. Compared with the prior art, the invention has the following remarkable advantages that the invention provides and verifies that the activin A can promote the repair and regeneration of nerve injury through the synergic regulation and control of schwann cells and neurons for the first time, and provides a new direction for the treatment of diseases caused by nerve injury. Drawings FIG. 1 is a graph showing the results of neuronal protrusion length detection after co-culturing with Schwann cells, wherein A is a representative image, scale bar is 100 μm, and B is a statistical graph of relative axon total length; FIG. 2 is a graph showing the effect of recombinant protein of Activin A on cell migration after injury of sciatic nerve, wherein A is a representative image, the scale is 1000 μm, and B is a statistical graph of relative fluorescence intensity; FIG. 3 is a graph showing the effect of recombinant protein of Activin A on regeneration of damaged nerve after injury of the sciatic nerve, wherein A is a representative image, the scale is 1000 μm, and B is a statistical graph of average axon regeneration length. Detailed Description The technical scheme of the invention is further described below. EXAMPLE 1 use of activin A for Schwann cell and neuronal Co-culture 1. Isolation, culture and treatment of primary schwann cells Sciatic nerves of neonatal SD rats were harvested, digested with collagenase I at a concentration of 3mg/mL at 37℃for 30min after vascular membrane removal, digested with 0.25% pancreatin at 3