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A small molecular polypeptide and its application in the preparation of drugs for preventing and treating Parkinson's syndrome

A Parkinson's and drug technology, applied in the application field of small molecular peptides in the preparation of drugs for the prevention or treatment of Parkinson's syndrome, can solve the problems that patients can only be treated symptomatically, cannot be effectively cured, and have limited treatment methods

Active Publication Date: 2021-05-18
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In 2015, there were 6.2 million Parkinson's patients in the world, and 117,400 patients died. However, the current treatment methods for Parkinson's syndrome are very limited, and the existing drug treatment and surgical treatment cannot be effectively cured, so most patients can only Symptomatic treatment

Method used

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  • A small molecular polypeptide and its application in the preparation of drugs for preventing and treating Parkinson's syndrome
  • A small molecular polypeptide and its application in the preparation of drugs for preventing and treating Parkinson's syndrome
  • A small molecular polypeptide and its application in the preparation of drugs for preventing and treating Parkinson's syndrome

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Synthesis of TAT-pSyn

[0032] The sequence of TAT-pSyn is shown as SEQ ID NO.1, which was artificially synthesized by Jiangsu Qiangyao Biotechnology Co., Ltd. The synthesis report is as follows, and the chromatogram is as follows figure 1 shown.

[0033] TAT-pSyn synthetic HPLC report

[0034] Product name: 04010035452 Peptide name: TAT-pSyn Measurement: Peak Area Calculation Type: Percentage Injection volume: 10 microliters Passing time: 11 minutes Chromatographic column: Kromasil 100-5C18, 4.6mm*250mm, 5micron Flow rate: 1ml / min Solvent A: 0.1% TFA in water Column temperature: 25°C Solvent B: 0.1% TFA in Acetonitrile Wavelength: 220nm Solvent gradient: 15%-35% buffer B in 11min

[0035] wavelength time Peak area Peak Area Percentage (%) 1 220nm 7.680 92944 4.21 2 220nm 8.063 2114477 95.79 total 2207421 100

[0036] The purity of the synthesized TAT-pSyn poly...

Embodiment 2

[0040] TAT-pSyn blocks the combination of DAPK1 and alpha-synuclein, and inhibits the hyperphosphorylation and abnormal aggregation of alpha-synuclein.

[0041] Culture neurofibroma blastocytes (N2a) in vitro, transfect eukaryotic expression plasmids of alpha-synuclein, and give 0uM, 5uM, 25uM, 50uM TAT-pSyn polypeptide or control TAT- s-pSyn polypeptide or vehicle incubation. Cellular proteins were extracted after 90 minutes. The result shows: after giving the TAT-pSyn of 25uM, the protein amount of alpha-synuclein and the alpha-synuclein of phosphorylation all reduce ( figure 2 ). It suggested that TAT-pSyn blocked the interaction between DAPK1 and alpha-synuclein, thereby inhibiting the hyperphosphorylation and abnormal aggregation of alpha-synuclein.

Embodiment 3

[0043] Application of TAT-pSyn in transgenic mouse model of Parkinson's syndrome

[0044] (1) Establishment of Parkinson's syndrome mouse model

[0045] The Alpha-synuclein (A53T) transgenic mice with the number 004479 were purchased from Jackson Lab in the United States for breeding. Mouse prion promoter. At eight months, some of the homozygous mice progressively developed severe movement impairments. The phenotype emerges by an average of 14-15 months. Skin laxity, weight loss and bradykinesia preceded by dyskinesia, partial paralysis, tremor, and inability to stand. Immunohistochemical analysis of 8- to 12-month-old mutant mice revealed aggregated synuclein inclusions in the spinal cord, brainstem, cerebellum, and striatum. Malignant aggregation of synuclein goes hand in hand with development of movement disorders We used 12-month-old mice as experimental model mice.

[0046] (2) Intravenous injection of TAT-pSyn

[0047] 12-month-old Alpha-synuclein (A53T) model mic...

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Abstract

The invention discloses a small molecule polypeptide TAT‑PSYN and its application in the preparation of drugs for preventing or treating Parkinson's syndrome. By synthesizing the fusion protein TAT-pSyn of the TAT protein transduction domain and the protein polypeptide that can bind to and inhibit the synuclein (alpha-synuclein), the pSyn protein polypeptide is transported through the blood through the blood-brain barrier by TAT, and is neuron Yuan uptake. Applying the polypeptide to the Alpha‑synuclein (A53T) transgenic mouse model of Parkinson’s disease can effectively block the combination of synuclein (alpha‑synuclein) and death-associated protein kinase 1 (DAPK1), and inhibit the α‑synuclein (alpha‑synuclein) The loss of dopamine neurons and nerve projections caused by synuclein phosphorylation and abnormal aggregation can reduce the dyskinesia of Parkinson's model, and provide molecular targets for clinical treatment of Parkinson's syndrome drugs.

Description

technical field [0001] The invention belongs to the field of medicine and biotechnology, and relates to drugs for preventing and treating Parkinson's syndrome, in particular to the application of small molecule polypeptides in the preparation of drugs for preventing or treating Parkinson's syndrome. Background technique [0002] In 1817, British doctor James Parkinson first described Parkinson's syndrome in detail. Its clinical manifestations mainly include resting tremor, slow movement, muscle rigidity, and posture and gait disorders. At the same time, patients may be accompanied by depression, constipation, and sleep disorders. non-motor symptoms. The prominent pathological changes of Parkinson's disease are the degeneration and death of dopamine (DA) neurons in the substantia nigra of the midbrain, the significant reduction of DA content in the striatum, and the appearance of eosinophilic inclusion bodies in the cytoplasm of the remaining neurons in the substantia nigra, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/00A61K38/16A61P25/16
CPCA61K38/00C07K14/00
Inventor 朱铃强邓曼菲刘丹周雅帆谢傲吉
Owner HUAZHONG UNIV OF SCI & TECH
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