疾患モデルを用いて創薬標的分子の発見及びその実用化を目指す。 Elucidation of the mechanism underlying both neuronal cell death and vascular lesions and the development of therapeutic drugs for them
「神経細胞死及び血管病変の機序解明並びにその治療薬開発」が本研究室の研究テーマである。神経細胞死にはアポトーシスが深く関与しており、酸化ストレス、小胞体ストレスなどの関与が示唆されている。また、血管新生や血管透過性亢進などの血管病変には vascular endothelial growth factor （VEGF）を含む多くの因子が関与するが、その分子メカニズムの詳細は解明されていない。そこで、分子生物学的並びに薬理学的な手法を用いて、神経細胞死のpoint of no return の分子機構並びにその決定要因を明らかにすることを目的に、脳卒中、鬱病などに代表される中枢神経疾患及び緑内障、加齢黄斑変性などの眼疾患に関する病態解明並びに治療薬開発の基礎的な研究を行っている。各種動物モデルを確立し、諸種の遺伝子改変動物や臨床サンプルを用いて、病態形成に関わる生体機能因子の探求並びに機構の解析を行っている。さらには、健康食品やサプリメントの新たな薬理作用に関する研究も行っている。
"Elucidation of the mechanism underlying both neuronal cell death and vascular lesions and development of therapeutic drugs for them" is the theme of our research laboratory. Apoptosis is involved in neuronal cell death, and it has been suggested that oxidative stress and endoplasmic reticulum (ER) stress participate as the underlying mechanisms. In addition, many factors, including vascular endothelial growth factor (VEGF), are involved in vascular lesions, such as angiogenesis and increased vascular permeability, but the molecular mechanisms of their involvement have not been elucidated in detail. By using the molecular biological and pharmacological approaches, we are studying to clarify the molecular mechanisms and determinants for "point of no return" in neuronal cell death, and conducting basic research for elucidating the pathological mechanisms and the development of therapeutic drugs in central nervous diseases (stroke and depression) and ocular diseases (glaucoma and age-related macular degeneration). We also have a variety of established animal models and are analyzing biofunctional molecules related to pathological processes and their mechanisms using clinical samples and genetically modified animals. Furthermore, we are conducting researches on new pharmacological effects and their mechanisms on health foods and supplements.
研究課題 Research Objectives
緑内障、加齢黄斑変性、網膜静脈閉塞症などの眼疾患に関する病態解明及び創薬研究 Studies for elucidating pathological mechanisms and drug discovery on ocular diseases such as glaucoma, age-related macular degeneration and retinal vein occlusion
脳卒中及び精神疾患などに代表される中枢性疾患に関する病態解明及び創薬研究 Studies for clarifying pathological mechanisms and drug discovery on CNS diseases such as stroke and psychiatric disorders
iPS 細胞など幹細胞を用いた病態解明及び創薬研究 Studies for elucidating pathological mechanisms and drug discovery using stem cells including iPS cells
健康食品及びサプリメントの新規薬理作用に関する研究 Studies on new pharmacological effects of health foods and supplements
最近の研究成果 Research Results
Tanaka M., Nakamura S., Sakaue T., Yamamoto T., Maekawa M., Nishinaka A., Yasuda H., Yunoki K., Sato Y., Sawa M., Yoshino K., Shimazawa M., Hatano M., Tokuhisa T., Higashiyama S., Hara H. BCL6B contributes to ocular vascular diseases via Notch signal silencing. Arterioscler Thromb Vasc Biol., in press (2023).
Hirakida H., Okumura T., Fujita R., Kuse Y., Mizoguchi T., Inagaki S., Nakamura S., Shimazawa M., Hara H. VGF nerve growth factor inducible has the potential to protect pancreatic β-cells. Journal of Endocrinology, in press (2023).
# Oka N., # Van T. H. Doan, Matsubara H., Imai T., Yoshioka Y., Katsuki J., Fujii S., Nakamura S., Shimazawa M., Hara H., and Sakurai K. (# Contributed equally). Protective effects of alpha-mangostin encapsulated in cyclodextrin-nanoparticle on cerebral ischemia. Journal of Controlled Release, 353, 216-228 (2023).
Nishinaka A., Tanaka M., Ohara K., Sugaru E., Shishido Y., Sugiura A., Moriguchi Y., Toui A., Nakamura S., Shimada K., Watanabe S., Hara H., Shimazawa M. TRPV4 channels promote vascular permeability in retinal vascular disease. Experimental Eye Research, 228, 109405 (2023).
Aoshima K., Inagaki S., Nakamura S., Hara H., Shimazawa M.ALK5 inhibitor acts on trabecular meshwork cell and reduces intraocular pressure. Experimental Eye Research, Volume 227, 109382 (2023).
Hidaka Y., Nakamura S., Nishinaka A., Takajo Y., Inamasu S., Yomoda S., Shimazawa M., Hara H.Arctigenin prevents retinal edema in a murine retinal vein occlusion model. Biological and Pharmaceutical Bulletin, 46, 3, 473-481 (2023).
