2023-10-19 07:53:01
DGIST, Kyungpook National University, and KIOM produce astroglial cells using pluripotent stem cells and conduct related research.
DGIST Neuroscience Department Professor Jinsoo Seo (from left), Hyein Lee, integrated master’s and doctoral student, and Sookhee Jo, senior manager at Illimi Therapeutics / DGIST
Daegu Gyeongbuk Institute of Science and Technology (DGIST) announced on the 19th that Professor Seo Jin-soo’s team in the Department of Neuroscience discovered the glucose metabolism function of astrocytes by the ‘APOE4 genotype’, a strong risk factor for Alzheimer’s dementia.
It is expected to contribute to the prevention of Alzheimer’s dementia and the development of new treatments. This study was conducted by Professor Lee In-gyu of Kyungpook National University School of Medicine and Dr. Ko Young-hoon’s team from the Korea Institute of Oriental Medicine (KIOM).
The APOE4 genotype is found in approximately 20% of the general population without dementia. However, it is observed at a rate of more than 50% in Alzheimer’s dementia patients and is known to be one of the major genetic factors causing dementia.
Research on the role of APOE4 in relation to the development of Alzheimer’s dementia is being conducted in various fields, but the answer has not yet been found as to why the APOE4 genotype causes decline in brain function in old age.
To investigate this, the joint research team created astroglial cells using pluripotent stem cells derived from humans and conducted related research.
As a result, it was confirmed that among the sugar metabolism processes of the APOE4 genotype, the rate of glycolysis (a metabolic process that obtains energy by breaking down glucose without oxygen) specifically increased and mitochondrial respiration decreased.
We observed that this change was due to the accumulation of cholesterol in lysosomes and the failure of damaged mitochondria to be properly decomposed, and it was confirmed that when cholesterol accumulation is resolved, lysosomal function and mitochondrial decomposition are normalized.
Professor Seo Jin-su said, “If the APOE4 genotype reduces the mitochondrial respiration ability of astrocytes, it may have a greater adverse effect on brain function in old age than in adulthood.” He added, “This study confirms that normal mitochondrial respiration is restored through restoration of lysosomal function.” “We hope that treatments using this will be developed in the future.”
This research was conducted through the Ministry of Science and ICT’s mid-career researcher project, brain science source technology development project, Korea Brain Research Institute basic project, Korea Institute of Oriental Medicine basic project, DGIST Grand Challenge Research Innovation Project (P-CoE), and the Ministry of Health and Welfare and Science and Technology Information. It was carried out with support from the Dementia Overcome Research and Development Project of the Ministry of Communications.
This paper, in which Hyein Lee, a combined master’s and doctoral student in the Department of Neuroscience at DGIST, and Sookhee Jo, a postdoctoral researcher (currently senior manager at Illimi Therapeutics) participated as first authors, was recently published online in the international academic journal ‘Cell Reports’.
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