CN-122012396-A - Organelle for promoting nerve tube closure and extraction method and application thereof

Abstract

The invention belongs to the technical field of biological medicines, and particularly discloses a organelle for promoting nerve tube closure, and an extraction method and application thereof. The organelle promoting the closure of the nerve tube is named as a plastic body, is positioned in a vesicle-shaped structure of a polar region of nerve epithelial cells, has a diameter of about 500-2000nm and comprises characteristic protein components such as RACK1, HNRNPA and the like. The invention includes methods of identification and extraction of the plastic body, methods of promoting its production by modulating the expression of RACK1 and HNRNPA, and therapeutic compositions and methods developed based thereon for promoting physiological closure of tissue structures such as neural tubes. The invention provides the application of the plastic body, key components and promoters thereof in preparing medicaments for treating neural tube deformity, and provides a brand-new targeted treatment strategy for related diseases.

Inventors

• DING DONGXUE
• YUAN ZHENGWEI
• WEI XIAOWEI
• MA WEI

Assignees

• 中国医科大学附属盛京医院

Dates

Publication Date

20260512

Application Date

20260212

Claims (9)

1. 1. An organelle promoting closure of a nerve tube, characterized in that it is a vesicle-like structure, designated as a plastic body, located in the polar region of a neuroepithelial cell, has a diameter of about 500-2000 nm, and comprises RACK1 protein and HNRNPA protein.
2. 2. The organelle according to claim 1, wherein the shaping facilitates a planar to stereoscopic morphological transition of the neural plate, mediating coordinated movement of the neural epithelial cells.
3. 3. A method for preparing the molded body according to claim 1 or 2, comprising the steps of obtaining a neuroepithelial cell or embryonic neural tissue, subjecting to lysis, subjecting to differential centrifugation and flow separation in sequence, and collecting a target component to obtain the molded body.
4. 4. The method of claim 3, wherein the differential centrifugation conditions are centrifugation for 10 minutes at 200 g and 30 minutes at 3000 g, and supernatant is collected and resuspended in 1 XPBS by centrifugation for 30 minutes at 17200 g.
5. 5. A method for promoting the production of a plastic body by increasing the expression level or activity of RACK1 protein and HNRNPA protein in a target cell.
6. 6. The method of claim 5, wherein the target cell is a neuroepithelial cell or a neural stem cell.
7. 7. A pharmaceutical composition comprising an effective amount of RACK1 protein and HNRNPA protein, or nucleic acid encoding the same, and a pharmaceutically acceptable carrier.
8. 8. A pharmaceutical composition comprising the shaped body of claim 1 or 2, and a pharmaceutically acceptable carrier.
9. 9. Use of a pharmaceutical composition according to claim 7 or 8 for the preparation of a medicament for the prevention or treatment of a neural tube deformity.

Description

Organelle for promoting nerve tube closure and extraction method and application thereof Technical Field The invention relates to the field of biomedicine, in particular to a organelle for promoting nerve tube closure, and an extraction method and application thereof. Background In the processes of embryo development and tissue organ formation, cell populations derived from stem cells construct complex three-dimensional functional structures by self-organization. The process has high dynamic property and diversity, and relies on the space-time precise regulation and control of various development signal paths to coordinate the biological behaviors of cell proliferation, morphological change, migration, adhesion and the like. However, in three-dimensional space, whether there is a specific subcellular structure capable of integrating multicellular collective motion to actively shape complex organ morphology remains a scientific problem that has not been solved in the art. At present, research on tissue morphogenesis mechanisms is limited to two-dimensional or simplified models, and cell structures with clear morphogenetic promoting functions at three-dimensional stereo layers have not been reported. The neural tube is a key structure formed in early development of the central nervous system, and the closing process is tightly regulated. Genetic factors or maternal exposure to adverse conditions (e.g., infection, radiation, malnutrition, etc.) can cause nerve tube insufficiency, leading to severe nerve tube deformities such as spinal fissures, brain failure, etc. The neonatal morbidity of the disease is about 0.1%, which is one of the congenital defects with highest mortality rate. About 70% of the neural tube abnormalities are related to genetic factors, and closure requires coordinated expression of a large number of genes in a specific space-time. Although studies have identified hundreds of genes associated with neural tube defects, single or combination gene therapy has limited efficacy against complex cases caused by multiple etiologies. At present, the intervention for the neural tube deformity mainly comprises two strategies of prevention and surgical repair, and obvious limitations exist. In terms of prevention, folic acid supplementation during pregnancy is effective as a primary prevention means for about 70% of cases, but still about 30% belong to "folic acid resistance", and its effect is limited only to the critical window of nerve tube closure (within 28 days after conception), failing to reverse the deformity that has formed. In the aspect of repair, although surgical operations (including intrauterine or postpartum operations) can physically close defects and reduce the risks of hydrocephalus and the like, the surgical operations are still "physical repair" in nature, the damaged nerve functions cannot be recovered, and the problems of high risk, large wound and the like are accompanied with maternal-fetal operations. In addition, although the emerging regenerative medicine means such as stem cell therapy has the potential of promoting regeneration in theory, the safety and effectiveness challenges of tumorigenicity, immune rejection, low cell survival rate, strict ethical supervision and the like exist, and although the technologies of tissue engineering, 3D biological printing and the like can construct a three-dimensional structure, the dynamic simulation and the guidance of cells to autonomously complete the accurate morphogenesis process are still difficult. In summary, how to realize the direct and accurate regulation of the three-dimensional morphogenesis ability of neuroepithelial cells to promote the autonomous and physiological closure of the neural tube remains a core problem not overcome in the prior art. Therefore, a targeting strategy capable of directly energizing nerve epithelial cells and remodelling the three-dimensional morphogenesis capability of the nerve epithelial cells is developed to fill the fundamental blank of the existing treatment mode, and has important significance. Disclosure of Invention Aiming at the problems existing in the prior art, the invention provides a organelle for promoting nerve tube closure, and an extraction method and application thereof. The invention separates and extracts the plastic body in tissue organ and cell, and defines the main molecule generated by plastic body, and promotes the expression of RACK1 and HNRNPA 1in tissue cell to promote the generation of plastic body by adenovirus transfection, thereby promoting the morphological generation of nerve tube, and having important significance for nerve tube malformation. In order to achieve the above object, the present invention provides the following technical solutions. The invention discloses a cell device for promoting nerve tube closure, which is characterized in that the cell device is a vesicle-shaped structure named as a plastic body, is positioned in a polar region of nerve epit