Application of ApoE receptor protein oligopeptide blocker in Alzheimer's disease

Abstract

The invention discloses an application of an ApoE receptor protein oligopeptide blocker in the Alzheimer's disease, and relates to the field of synthetic protein peptide drugs. The invention disclosesan application of modified peptides after an amino acid sequence and lysine of synthetic oligopeptides ApoEp for inhibiting an ApoE receptor is modified into 6KApoEp and C-16 fatty acid, namely, palmitic acid containing double bonds is modified into C6KApoEp in prevention and treatment of the Alzheimer's disease, meanwhile, it is detected that the fused oligopeptides are specifically targeted toblock the interaction between exogenous and endogenous ApoE and N-terminals of amyloid precursor proteins (APP) according to the molecular, cellular and animal levels, and finally, the C6KApoEp seriesoligopeptides are administered in an intranasal administration manner to prevent and treat the Alzheimer's disease. On the basis of focusing on research of AD morbidity mechanism and treatment for more than 20 years, a scientific research group proposes a novel hypothesis capable of blocking ApoE-mediated APP excessive endocytosis and beta-cleavage and A[beta] generation processes so as to perform treatment in multiple pathophysiologic links of the AD for the first time.

Description

technical field [0001] The invention relates to the field of synthetic protein peptide drugs, in particular to the application of a class of ApoE receptor protein short peptide blockers in Alzheimer's disease. Background technique [0002] As we all know, Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset and progressive development. It is also one of the most common types of dementia among the elderly in the world and one of the important causes of death. At present, there are about 8.75 million AD patients in my country, and the resulting social and economic burden is close to 200 billion US dollars; it is estimated that by 2030, the total number of AD patients in my country will be More than 20 million, AD is difficult to diagnose early, and there is no specific preventive and therapeutic drug, which has caused a heavy burden and huge economic pressure to the family and society. [0003] AD is divided into two types: familial Alzheimer's disease (...

AI Technical Summary

Problems solved by technology

[0006] Whether at home or abroad, finding new targets for the treatment of AD is still the latest research hotspot. Most of the previous research focused on the following two directions: ①APPβ-cleavage and excessive production of Aβ aggregated to form senile plaques, resulting in neuronal cell apoptosis , neuroinflammation and oxidative stress in the pathophysiological mechanism of AD; ② explore the role of ApoE in increasing the formation of Aβ and reducing the clearance of Aβ to promote the disease process of AD, although some recent important discoveries have highlighted other key cells and The important pathological role of molecular processes, however, with the failure of the research and development of AD treatment projects, there is no effective treatment to improve the disease, and many phase III clinical trials have not proved its benefits. Therefore, closely surrounding the pathophysiology of AD To change and explore new key cellular and molecular processes from multiple perspectives is a new strategy for the prevention and treatment of AD

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