PP2A agonist for preventing and treating mental disorders caused by normal aging or reduction of PP2A activity or expression

A mental disorder and agonist technology, applied in the field of mental disorders, can solve problems such as ambiguous PP2A relationship, no PP2A agonist PP2A activity or expression of mental disorders, and achieve the effect of eliminating DNA damage

Active Publication Date: 2021-11-09
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Abstract
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Problems solved by technology

[0004] In general, the relationship between PP2A and neurological and psychiatric diseases is not clear at present, and there are no reports on the prevention and treatment of PP2A agonists in the prevention and treatment of mental disorders caused by normal aging or the reduction of PP2A activity or expression

Method used

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  • PP2A agonist for preventing and treating mental disorders caused by normal aging or reduction of PP2A activity or expression
  • PP2A agonist for preventing and treating mental disorders caused by normal aging or reduction of PP2A activity or expression
  • PP2A agonist for preventing and treating mental disorders caused by normal aging or reduction of PP2A activity or expression

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Embodiment 1

[0057] 1. Experimental method

[0058]1. All drug solutions were freshly prepared using PBS (MPH 1.08mg / kg, sodium valproate 300mg / kg, aripiprazole 0.6mg / kg, ziprasidone 1.6mg / kg, DT061 and FTY720 5mg / kg) . Zebrafish were given food soaked in the drug solution for 3 days and behavioral assays were performed on day 4. Both 14- and 3-month-old C57B6 / J mice were produced and maintained in the animal facility of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University. The protocol was approved by the Animal Experimentation Ethics Committee. 14-month-old and 3-month-old C57B6 / J mice were given MPH (12.3mg / kg / d) by intragastric administration for 14 days.

[0059] 2. Generation of CRISPR-Cas9 mutant zebrafish. The ppp2r2c mutant zebrafish was generated using the CRISPR-Cas9 system, in which the ppp2r2c exon 9 (sgRNA: 5′-GGGCAGAGATACC-3′( SEQ ID NO: 1)) and cdkn1a / p21 exon 2 (sgRNA: 5'-GGTAATGGGCCGACTAGG-3' (SEQ ID NO: 2)) guide RNA. The F0 generation was bred to 3 m...

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Abstract

The invention relates to a PP2A agonist for preventing and treating mental disorders caused by normal aging or reduction of PP2A activity or expression. The inventor of the invention finds that MPH has a treatment effect on mental disorders of old zebrafish, old mice and ppp2r2cm / m mutant zebrafish, can eliminate DNA damaged and senile nerve cells of the old zebrafish, the old mice and the ppp2r2cm / m mutant zebrafish and improve PP2A activity, and further finds that the PP2A agonist can improve the mental disorders of the ppp2r2cm / m zebrafish, the old zebrafish and the old mice and eliminate DNA damaged and senile nerve cells of the old zebrafish, the old zebrafish and the old mice. On the basis, the invention provides an application of MPH and PP2A agonists to preparation of medicines for preventing and treating mental disorder caused by normal age increase or PP2A activity reduction.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the prevention and treatment of mental disorders caused by normal aging or PP2A activity or expression reduction by PP2A agonists. Background technique [0002] Protein phosphatase 2A (protein phosphatase 2A, PP2A) is a serine / threonine phosphatase with a wide range of substrates, most of which involve transcription factors and protein kinases, and participate in many cell biological functions, such as energy metabolism, DNA damage It plays an important role in repair, protein translation, cell cycle regulation and signal transduction. Previous studies have shown that PP2A has a tumor suppressive effect; it is involved in the regulation of sugar and lipid metabolism, and abnormal PP2A function can lead to diabetes, obesity, etc. At the same time, coronary atherosclerosis is also related to the abnormal variation of PP2A; it is involved in retinopathy and cardiomyopathy and o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/4458A61K31/137A61K31/538A61P25/28A61P25/24A61P25/22A61P25/00A61P25/18
CPCA61K45/00A61K31/4458A61K31/137A61K31/538A61P25/28A61P25/24A61P25/22A61P25/00A61P25/18
Inventor 叶静陆一鸣陈科桦G·埃里克王波邢骏应亦林梁惠欣
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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