Chimeric molecule for mediating Tau protein degradation based on autophagy mechanism and application of chimeric molecule

A chimeric molecule and protein degradation technology, applied in the fields of hybrid peptides, organic chemistry, fusion polypeptides, etc., can solve the problem that it is difficult to efficiently degrade Tau protein aggregates, etc., to overcome the inability to efficiently degrade intracellular macromolecular components. Effect

Active Publication Date: 2020-07-14
CHONGQING UNIV
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Problems solved by technology

Since phosphorylated Tau protein tends to form aggregates, it also makes it diffi...

Method used

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  • Chimeric molecule for mediating Tau protein degradation based on autophagy mechanism and application of chimeric molecule
  • Chimeric molecule for mediating Tau protein degradation based on autophagy mechanism and application of chimeric molecule
  • Chimeric molecule for mediating Tau protein degradation based on autophagy mechanism and application of chimeric molecule

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Embodiment 1

[0037] 1. Construction of EGFP-Tau and EGFP-TauP301L fusion protein (target protein) expression vector

[0038] (1) PCR amplification of the full-length nucleic acid fragment of the Tau protein, extracting the DNA of the plasmid pET28a-Tau (containing the full sequence of the wild-type Tau protein) as an amplification template: The PCR reaction system is: 2×PCR Bestaq TM MasterMix with dye12.5μl, upstream primer Tau-F 1μl, downstream primer Tau-R 1μl, DNA template 1μl, add 9.5μl ddH 2 O to a final volume of 25 μl. Refer to Table 1 for primer sequences. The full-length nucleic acid sequence of the wild-type Tau protein is shown in SEQ ID NO:1.

[0039] Table 1. Tau protein full-length nucleic acid sequence PCR amplification primers

[0040]

[0041] The PCR reaction program was: pre-denaturation at 95°C for 5 min; denaturation at 95°C for 30 s, annealing at 58°C for 30 s, extension at 72°C for 1 min, and 32 cycles of reaction; extension at 72°C for 10 min, and the PCR pr...

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Abstract

The invention discloses a chimeric molecule for mediating Tau protein degradation based on an autophagy mechanism, and the amino acid sequence is shown in SEQ ID NO:5 or 7. The invention also discloses a nucleic acid molecule and an expression vector; and the nucleic acid molecule is used for encoding the chimeric molecule for mediating Tau protein degradation based on the autophagy mechanism, andthe expression vector comprises the nucleic acid molecule. The invention also discloses an application of the chimeric molecule for mediating Tau protein degradation based on the autophagy mechanism,the nucleic acid molecule and the expression vector in degradation of Tau protein. The novel targeted chimeric molecule is developed in the invention, and the chimeric molecule is bound to the surface of the aggregate protein Tau, so that the Tau protein is recruited into cell autophagosome and is promoted to be degraded through the cell autophagy pathway. The novel protein targeted degradation technology provided by the invention is expected to be applied to different target proteins, so as to overcome the defect that a current ubiquitin-proteasome pathway-based protein targeted degradationtechnology cannot efficiently degrade intracellular macromolecules.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a chimeric molecule that mediates the degradation of Tau protein based on an autophagy mechanism and its application. Background technique [0002] Neurodegenerative diseases are a general term for a group of diseases characterized by the progressive loss of central neurons, and have attracted much attention because of their undruggability and serious impact on the quality of life of middle-aged and elderly patients. These include Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Studies have shown that the occurrence of most neurodegenerative diseases is accompanied by the abnormal accumulation of aggregates formed by misfolded proteins in nerve cells, which can have toxic effects on neurons. [0003] For this type of disease, currently clinically, small molecule inhibitors are mainly used to bind to the active si...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N15/62C12N15/85C12N5/10C07K1/12
CPCC07K1/12C07K14/4702C07K2319/00C12N15/85
Inventor 杨爱民梅礼刚林昌海
Owner CHONGQING UNIV
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