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Home » Okayama University Astrocyte function switch by lipid signal SphK2/S1P! ~ Expectations as a multifunctional therapeutic target for Alzheimer’s disease ~

Okayama University Astrocyte function switch by lipid signal SphK2/S1P! ~ Expectations as a multifunctional therapeutic target for Alzheimer’s disease ~

National University Corporation Okayama University
[Okayama University] Astrocyte function switch by lipid signal SphK2/S1P! ~ Expectations as a multifunctional therapeutic target for Alzheimer’s disease ~
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March 31, 2024 (Reiwa 6) National University Corporation Okayama University https://www.okayama-u.ac.jp/
[Image 1: https://prtimes.jp/i/72793/2095/resize/d72793-2095-91736ca44439B7-0.jpg &s3=72793-2095-b9a9C5BC6D16E345B2A2CEFD385B 2D6D-1950×1106.jpg] -Key points of presentation-
At the time of diagnosis, Alzheimer’s disease (AD) is considered to be a complex disease with pathological conditions such as neuronal damage and astrocyte activation that induces chronic inflammation.
In this study, we demonstrated that regulation of gene expression by signal lipids may have a switch function that changes the function of astrocytes from defensive to offensive.
The results of this research are expected to lead to the development of multifunctional treatments that can simultaneously treat multiple pathological conditions in AD, including pathological conditions of astrocytes and neurons.

◆Overview
Masato Komai, a graduate student in the doctoral course at the Graduate School of Biomedical Sciences, National University
Corporation Okayama University (Headquarters: Kita-ku, Okayama City, President: Yasutomo Nasu); Associate Nobumasa Takasugi, Faculty of Biomedical Sciences, Okayama University Academic Research Institute In joint research with Juntendo University, the professor’s group focused on changes in astrocyte function in AD and elucidated the mechanism by which the expression of Apolipoprotein-E (ApoE), a genetic risk factor for AD, is regulated by lipid signals.
AD is a progressive neurodegenerative disease, and there is strong support for the “amyloid hypothesis,” which posits that the disease is caused by metabolic abnormalities and aggregation of amyloid-β (Aβ), which accumulates in patients’ brains like rust on metal.
On the other hand, the efficacy of therapeutic drugs based on hypotheses is limited, and the reason for this is that multiple pathological conditions coexist, including changes in the function of astrocytes, which have functions such as regulating brain immunity, in addition to Aβ aggregation. .
In this study, we investigated the effects of sphingosine kinase 2 (SphK2), whose activity increases in AD, and its produced lipid, sphingosine-1-phosphate (S1P), on astrocyte pathology.
ApoE is a lipid transport mediator with anti-inflammatory and Aβ metabolic effects, and its expression decreases in astrocytes in AD pathology.
We found that increased SphK2 activity acts offensively by suppressing ApoE expression and promoting inflammatory reactions, whereas SphK2 inhibitors act defensively by increasing ApoE expression, suppressing inflammatory reactions, and promoting Aβ uptake, and SphK2/S1P signals are We discovered that it has the role of “switching” site
functionality.
This research result proposes a mechanism in which specific gene expression is regulated by lipids, and together with the finding that SphK2 inhibitors suppress Aβ production in nerve cells, which our research group reported, SphK2/S1P signals are This shows the potential to be a target for multifunctional therapeutic agents that simultaneously control the functions of neurons and astrocytes. This information was released by Okayama University on March 27, 2024.
[Image 2: https://prtimes.jp/i/72793/2095/resize/d72793-2095-28db305429620fedf3f8-1.jpg&s3=72793-2095-5cbb097d9f3a9139800139ef38ca191e-800×546.jpg]
[Image 3: https://prtimes.jp/i/72793/2095/resize/d72793-2095-aacc24fb540463d68569-2.jpg&s3=72793-2095-f549d09b174c5ee3633ab04e5ad816da-800×536.jpg] ◆A message from graduate student Masato Komai
It has been about 6 years since I took over the theme from my predecessor. I am very happy that I was able to put all the data I had accumulated through my time with cells into a single form. Although S1P has some properties that are difficult to handle, I think it is an interesting molecule with many possibilities.
Although this research is still in its infancy toward a complete cure for the disease, we would be happy if we could make even a small contribution to “Alzheimer’s disease treatment through lipid control.” We would like to express our deepest gratitude to everyone involved.
[Image 4: https://prtimes.jp/i/72793/2095/resize/d72793-2095-7b1fbe40bd982bce1d40-3.jpg&s3=72793-2095-af4bb3a3dbc2b1888211823973c0d491-136×141.jpg] Masato Komai Graduate Student
◆Paper information Paper title: Nuclear SphK2/S1P signaling is a key regulator of ApoE production and Aβ uptake in astrocytes. Publication paper: Journal of Lipid Research Author: Komai M, Noda Y, Ikeda A, Kaneshiro N, Kamikubo Y , Sakurai T, Uehara T, Takasugi N. D O I: 10.1016/j.jlr.2024.100510. U R L:
https://www.sciencedirect.com/science/article/pii/S0022227524000154?via=ihub ◆Research funding This research was supported by the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (Grants-in-Aid for Scientific Research (C); 26430059, 17K08272, 20K07014, Fundamental Research (B); 21H02815, JSPS Fellowship; 23KJ1603, This work was supported by the Japan Science and Technology Agency (JST) (JPMJFS2128).
◆About detailed research content Astrocyte function switch by lipid signal SphK2/S1P! ~ Expectations as a multifunctional therapeutic target for Alzheimer’s disease ~
 https://www.okayama-u.ac.jp/up_load_files/press_r5/press20240327-4.pdf ◆Reference ・Okayama University Graduate School of Biomedical Sciences (Pharmaceuticals) Drug Efficacy Analysis Laboratory
https://www.okayama-u.ac.jp/user/yakko/index.html ・Okayama University School of Pharmacy/Graduate School of Medicine and Dentistry Graduate School of Pharmaceutical Sciences (Pharmacy)
https://www.pharm.okayama-u.ac.jp/
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Okayama University Tsushima Campus, 1-1-1 Tsushima Naka, Kita-ku, Okayama City, Okayama Prefecture 700-8530 TEL: 086-251-7985
https://www.okayama-u.ac.jp/user/yakko/index.html – Regarding collaboration with Okayama University Hospital (for those involved in pharmaceutical and medical device companies) – Okayama University Hospital New medical research and development Center: 2-5-1
Shikata-cho, Kita-ku, Okayama City, Okayama Prefecture, 700-8558 Please inquire about the applicable project from the URL below: http://shin-iryo.hospital.okayama-u.ac.jp/ph_company/-Okayama Regarding collaboration with university hospitals (for medical personnel and researchers) – Okayama University Hospital Research Promotion Division Industry-academia-government collaboration promotion 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558 TEL: 086 -235-7983 E-mail: ouh-csnw◎adm.okayama-u.ac.jp
http://shin-iryo.hospital.okayama-u.ac.jp/medical/- Regarding Okayama University’s industry-academia-government collaboration, etc. Contact information – Okayama University Research Promotion Organization Industry-Academia-Government Collaboration Headquarters 1-1-1 Tsushima Naka, Kita-ku, Okayama City, Okayama Prefecture 700-8530 Okayama University Tsushima Campus Main Building 1F TEL: 086-251-8463 E-mail: sangaku ◎okayama-u.ac.jp https://www.orsd.okayama-u.ac.jp/
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