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Application of ferroportin in the treatment of Parkinson's disease

A technology for patients with Parkinson's disease, applied in the field of gene-targeted drug preparation, to increase the activity of mitochondrial complexes, improve mitochondrial respiratory function, and improve muscle damage

Active Publication Date: 2022-08-02
HEFEI UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although some in vitro experiments show that iron ions may have a certain relationship with the pathogenesis of PD, there has been no more detailed and convincing evidence in vivo to prove

Method used

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  • Application of ferroportin in the treatment of Parkinson's disease
  • Application of ferroportin in the treatment of Parkinson's disease
  • Application of ferroportin in the treatment of Parkinson's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1: phylogenetic tree analysis

[0049] Phylogenetic tree analysis of human genes ZIP13 and Tsf and Drosophila genes dZIP13 and Tsf1 using MEGA software showed that Drosophila dZIP13 and human ZIP13, Drosophila Tsf1 and human Tsf belong to orthologous genes and have the same or similar functions ( Figure 1-2 ).

Embodiment 2

[0050] Example 2: Acquisition of Tsf1 RNAi and dZIP13OE transgenic Drosophila lines

[0051] 1. Using the genomic DNA of the wild-type Drosophila w1118 strain as a template, Tsf1 and dZIP13 were isolated and cloned by PCR, and then introduced into E. coli competent cells through enzyme digestion, ligation and transformation. Positive clones were obtained by colony PCR, plasmid digestion identification and sequencing identification.

[0052] 2. Using the wild-type Drosophila w1118 as the receptor, use microinjection technology to transform the constructed plasmid into the newborn eggs by p-element-mediated method. After the eggs develop into adults, assign the number of each fruit fly to w1118 Crossbreeding, the red eye of the progeny flies means the construction is successful.

Embodiment 3

[0053] Example 3: Effects of Drosophila dZIP13 and Tsf1 genes on PD-like behavior in PINK1-deficient Drosophila

[0054] 1. The effect of dZIP13 OE and Tsf1 RNAi on the exercise capacity of PD

[0055] In order to construct a genetic PD model, PINK1 RNAi flies were crossed with Mhc-Gal4 flies, and the progeny were PD flies with PINK1 knockdown in the muscle site. The flies were crossed with Mhc-Gal4, respectively, and the progeny were flies with dZIP13 OE or Tsf1 RNAi in the muscle site. Progeny Drosophila were collected, Mhc-Gal4>+ / + normal group Drosophila, Mhc-Gal4>PINK1 RNAi model group Drosophila, Mhc-Gal4>PINK1 RNAi; dZIP13 OE Drosophila and Mhc-Gal4>PINK1 RNAi; Tsf1 RNAi in Drosophila. The number of abnormal wings in each group was counted and compared with the total number of fruit flies to calculate the proportion of abnormal wing types. Each tube has the same number, and the number of jumps is counted. The results show( image 3 A-B): Muscle-specific dZIP13 OE (...

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Abstract

The present invention relates to the field of genetic engineering, in particular, the present invention relates to a target protein of Parkinson's Disease (PD) and its encoding gene and application, and particularly relates to the preparation of gene-targeted drugs for the above-mentioned key genes. The present invention provides the target genes ZIP13 and Transferrin (Tsf) of Parkinson's disease, and significantly alleviates or delays PD by overexpressing ZIP13 or interfering with Tsf by gene silencing. According to the present invention, the target protein of human PD includes the amino acid sequences shown in SEQ ID No. 5 and SEQ ID No. 6, and the gene includes the nucleus as shown in SEQ ID No. 7 and SEQ ID No. 8. nucleotide sequence. According to the target gene of the present invention, constructing an RNAi vector carrying the target gene can be used to improve the exercise ability of PD patients through gene silencing or gene overexpression, and slow down or prevent PD symptoms caused by knockdown of PINK1. This invention is expected to provide new therapeutic strategies and key targets for the treatment of hereditary PD.

Description

technical field [0001] The present invention relates to the field of genetic engineering, in particular, the present invention relates to a target protein of Parkinson's disease (Parkinson's Disease, PD) and its encoding gene and application, in particular to the preparation of gene-targeted drugs for the above-mentioned key genes. Background technique [0002] Parkinson's Disease (PD) is a neurodegenerative disease affecting human health. The classic motor symptoms of PD have been recognized as an essential component of the disease since its original description by James Parkinson in the 19th century, and were later relabeled by Jean-Martin Charcot. These patients often have muscle tremors, muscle rigidity, slow movements, writing disorders, unsteady gait, general weakness, stiff facial expressions, and depressed mood, making it difficult for patients to take care of themselves, bringing heavy psychological and economic burdens to their families, and serious Affect social ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/12C07K14/47C12N15/85A61K31/7105A61K48/00A61P25/16
CPCC07K14/47C12N15/85A61K31/7105A61K48/005A61P25/16
Inventor 肖桂然薛劲松韦田纪晓雯
Owner HEFEI UNIV OF TECH
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