[이데일리 강민구 기자] The Institute for Basic Science (IBS) announced that a research team led by Director Cheon Jin-woo of Nanomedicine Research Fellow and Research Fellow Min-seok Kwak, together with California State University Professor Young-wook Jeon, discovered the process of activating Notch receptor signaling that plays an important role in tissue development and the process of forming amyloid beta known to cause Alzheimer’s. 10 the day said
Notch signaling is an important cell-to-cell interaction that regulates cell division and neuronal development. Incorrect Notch signals cause various diseases. Amyloid beta, which is formed from amyloid precursor protein, accumulates in tissues, causes nerve damage, and is involved in the development of Alzheimer’s disease.
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Notch activation and amyloid beta formation occur through sequential cleavage of the Notch receptor, the amyloid precursor protein, by two different types of enzymes in the cell membrane. Relatively little is known regarding the molecular mechanisms by which these processes are precisely regulated spatiotemporally and the substrate specificity of enzymes.
The research team confirmed that adhesive synapses, a structure that controls junctions between cells, act as a spatial switch that determines the order of sequential cutting processes and is required for normal Notch signal control. It was also found that the Notch receptor-ligand (substance that binds to the receptor and regulates its activity) interaction and the first cleavage process of the receptor occur outside the adhesive junction structure, and the second cleavage process occurs inside the adhesive junction structure.
In the course of the research, using ‘Mechanogenetics’, a nanotechnology that can deliver mechanical, spatiotemporal stimulation to specific receptors, adhesive junctions recruit gamma secretase enzymes at high concentrations and access Notch receptors that have not undergone the first cleavage process. It was also confirmed that blocking
It was found that the Notch signal was not activated when the expression of the cadherin protein was eliminated by actual gene editing technology. When cadherin expression was suppressed in neural stem cells in the developing mouse brain, the stem cells differentiated into neurons abnormally quickly. This proves that the process of controlling the Notch signal by adhesive junctions is involved in the development of the nervous system.
The research team also found that when the formation of adhesive junctions was inhibited in cells expressing the amyloid precursor protein, the amount of amyloid beta formed was reduced. It showed that the formation of amyloid beta, known as the main cause of Alzheimer’s, can be inhibited by controlling the protein cleavage process.
Professor Jeon Young-wook said, “For the first time, we have suggested the molecular and cellular mechanisms of sequential cleavage of proteins required for Notch signal activation and amyloid beta formation.” Research Fellow Min-Seok Kwak also said, “We expect to contribute to cancer-related research by abnormal cell signal transmission and research on Alzheimer’s disease treatment through inhibition of amyloid beta formation.”
The research results were published online on December 2 last year in the international journal Nature Cell Biology.
