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Succeeded in real-time observation of the toxic process of the causative agent of Alzheimer's disease

2024-02-06 01:26

A joint research team from Tokyo University of Agriculture and Technology and Mie University succeeded in observing in real time how amyloid-β, the causative agent of Alzheimer's disease, changes into a toxic structure in an artificial cell membrane. They found that cholesterol in membranes promotes the change to toxic structures, and that catechins inhibit toxic structures.

Amyloid β (Aβ) has a high aggregation property and forms amyloid fibrils from monomers through intermediate polymers (oligomers). Among them, Aβ oligomers are known to have strong cytotoxicity. One of the cytotoxic mechanisms of oligomers is the formation of channels (pores that penetrate the cell membrane), which cause cell death by creating pores in the nerve cell membrane. The process was not confirmed.

The research team observed the process by which Aβ monomers aggregate in a lipid membrane (artificial cell membrane) to form a channel over a two-hour period by measuring channel current using a microdevice. We discovered that Aβ monomers aggregate and oligomerize in membranes, forming channels. Subsequent observations using an artificial cell membrane that mimics a nerve cell membrane revealed that cholesterol in the membrane promotes Aβ channel formation in the membrane. Furthermore, as a result of investigating the effect of EGCG, a type of catechin, which is an Aβ aggregation inhibitor, on Aβ channels, they found that EGCG not only inhibits Aβ aggregation but also the activity of channels formed in the membrane.

These results are expected to advance the elucidation of the interaction between Aβ and nerve cell membranes and contribute to the development of treatments for Alzheimer's disease. The research paper was published in Proceedings of the National Academy of Sciences Nexus (PNAS Nexus) on December 14, 2023.

Source: MIT Technology Review Editorial Department [MIT Technology Review Japan]