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Application of Rac1 activity inhibitor in preparation of drugs for treating Alzheimer disease

An Alzheimer's disease, active inhibitor technology, applied in drug combinations, organic active ingredients, biological testing, etc., can solve problems such as cell death and neuronal cytoskeleton changes

Inactive Publication Date: 2019-06-25
BEIJING JOEKAI BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

So far in the prior art, no one has linked Rac1 with AD from the perspective of forgetting. The existing literature has found from in vitro experiments that the toxic protein Abeta-42 that causes AD can activate Rac1, resulting in changes in the neuronal cytoskeleton. triggering cell death

Method used

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  • Application of Rac1 activity inhibitor in preparation of drugs for treating Alzheimer disease
  • Application of Rac1 activity inhibitor in preparation of drugs for treating Alzheimer disease
  • Application of Rac1 activity inhibitor in preparation of drugs for treating Alzheimer disease

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Embodiment 1

[0039] 1. The discovery of the mechanism of cognitive impairment caused by the treatment of AD by inhibiting Rac1 activity

[0040] Firstly, by Western Blot, we detected the activated form of Rac1 (Rac-GTP), total Rac1 (Total Rac) and internal control protein (Actin) in the hippocampus of AD patients. figure 1). Through data analysis, it was found that the activity of Rac1 in the hippocampus of AD was significantly higher than that of the hippocampus of healthy people (HC), that is, the ratio of Rac-GTP to Total Rac was significantly different, and the expression of total Rac1 was significantly higher in the two groups. There is no difference in the sample ( figure 2 ). In the AD mouse model (APP / PS1) of different ages, in the hippocampal tissue of 3-month-old APP / PS1 mice, the activity of Rac1 tended to increase, but there was no statistical difference. In the hippocampus of APP / PS1 mice, the activity of Rac1 was significantly increased ( image 3 ). Adding human pathog...

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Abstract

The invention provides an application of a Rac1 activity inhibitor in preparation of drugs for treating an Alzheimer disease. The Rac1 activity inhibitor can be: at least one of EHop-016, CS7171, JKF-034, Secramine, AZD0530, NSC23766, MBQ-167, AZA1, AZA197, Compound 19, ZINC08010136, ZINC07949036, 69391, 1A-116, ITX3, ITX1, CPYPP, GGTase1inhibitor(P61A6, Statins), EHT1864, Compound 1, MLS000532223, R-Ketorolac, OSU-3012, FL172, FRAX597, Phox-11, 187-1 and Wiskostatin. The invention protects the discovery of a mechanism for treating AD by inhibiting the activity of a forgetting regulatory molecule Rac1, and protects the application of a small molecule compound capable of inhibiting Rac1 activity in treating AD.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the treatment of cognitive impairment caused by Alzheimer's disease by inhibiting the activity of small G protein Rac1, and a small molecular compound that inhibits the activity of small G protein Rac1, that is, an inhibitor of Rac1 activity. Drug use in Alzheimer's disease. Background technique [0002] Alzheimer's disease (AD) is a neurodegenerative disease. Accelerated amnesia is considered a typical symptom of the disease, but the mechanism for treating AD by inhibiting amnesia has not been reported, and no small molecule compounds based on this mechanism have been reported. [0003] Rac1 (Ras-related C3botulinum toxin substrate) is a member of the small G protein Rho family. So far in the prior art, no one has linked Rac1 with AD from the perspective of forgetting. The existing literature has found from in vitro experiments that the toxic protein Abeta-42 that causes AD can activat...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61P25/28A61K31/4152A61K31/495G01N33/50
Inventor 杜书文谢作磊刘振宇姚蔚
Owner BEIJING JOEKAI BIOTECH
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