Development of dementia treatment drugs that inhibit the substance causing the entire family to suffer from a sad disease

Domestic researchers have succeeded in developing an inhibitor that prevents the formation of toxic substances that induce Alzheimer's disease (dementia).

The Korea Research Foundation announced that the research teams led by Professors Kim Joon-gon and Choi Tae-soo from Korea University, along with Professor William Goddard III from the California Institute of Technology, successfully designed peptide aggregation inhibitors capable of preventing misfolding and self-aggregation of amyloid beta proteins through international collaborative research.

Amyloid beta is the main protein component of the pathogenic fibrillar aggregates found in the brains of Alzheimer's disease patients. It is known that pathogenic fibrillar aggregates are formed through the self-aggregation of misfolded amyloid beta proteins, which exhibit toxicity.

Recently, as more research focuses on developing treatments that target the causative substances of Alzheimer's disease to achieve a fundamental cure, successful cases are also increasing.

 

This clinical success highlights that the key target in the development of Alzheimer's disease treatments, which had long been unable to develop effective therapies, is the pathogenic fibrils of amyloid beta.

The research team systematically analyzed the structural characteristics of amyloid beta proteins and designed peptide inhibitors to prevent self-assembly caused by misfolded structures.

To inhibit aggregation, a high concentration of peptide aggregation inhibitors must be present in greater amounts than amyloid beta proteins, and structural changes are necessary for stable complex formation. For effective aggregation inhibition, the shapes must fit well together, like the lock's groove and the key's protrusion, but in the case of amyloid beta proteins and peptide aggregation inhibitors, their irregular structures resulted in weak binding forces between them.

 

To overcome these limitations, we induced the formation of an antiparallel β-sheet structure to enable stable complex formation with the intrinsically disordered amyloid beta protein. As a result, the formation of pathogenic fibrils of amyloid beta protein was reduced compared to previously developed inhibitors, and a significant alleviation of cytotoxicity was observed.

It also demonstrated suitable performance for use in treatment and prevention, such as evaluating the ability to pass through the blood-brain barrier in test tubes and assessing plasma stability.

Professor Kim Joon-gon stated, "He elucidated the structural characteristics of amyloid beta proteins and proposed a rational design method for peptides that can form stable complexes," and he expressed hope that "this technology will become an important cornerstone in the development of treatments for Alzheimer's disease, both for therapy and prevention."

This research achievement, supported by the Ministry of Science and ICT and the National Research Foundation of Korea through mid-career researcher and postdoctoral domestic training programs, as well as the Sejong Science Fellowship support project, was published in the international chemistry journal 'Angewandte Chemie International Edition' on May 22.

 

 

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The day when Alzheimer's dementia is truly conquered is approaching.

 

I hope the day comes when dementia disappears ^^