笹栗 弘貴, M.D., Ph.D.

研究内容

人の脳機能は加齢に伴う脳内環境の変化とともに低下していきます。一方で、アルツハイマー病をはじめとする神経変性疾患では、正常な老化のプロセスから逸脱して特定の神経細胞が変性、脱落し、様々な神経症状を呈します。当研究室では、マウスモデルに加え、非ヒト霊長類であるマーモセットモデルを作製し、最新の技術で解析することにより、未知の神経変性疾患の病態を解明し、新規バイオマーカーや治療方法を開発することを目標としています。更に、これら神経疾患の研究を通じて、脳の正常老化のプロセスを解明することを目指します。

研究主分野

医歯薬学

研究関連分野

総合生物 / 生物学 / 病態神経科学 / 神経科学 / 分子生物学

キーワード

• 認知症
• アルツハイマー病
• 神経変性疾患
• 動物モデル
• 健康長寿

主要論文

「*」は、理研外のみでの成果です。

1. Watamura N, Sato K, Shiihashi G, Iwasaki A, Kamano N, Takahashi M, Sekiguchi M, Mihira N, Fujioka R, Nagata K, Hashimoto S, Saito T, Ohshima T, Saido TC, Sasaguri H.
   "An isogenic panel of App knock-in mouse models: Profiling β-secretase inhibition and endosomal abnormalities."
   Science Advances. 8(23):eabm6155. (2022)
2. Sasaguri H, Hashimoto S, Watamura N, Sato K, Takamura R, Nagata K, Tsubuki S, Ohshima T, Yoshiki A, Sato K, Kumita W, Sasaki E, Kitazume S, Nilsson P, Winblad B, Saito T, Iwata N, Saido TC.
   "Recent Advances in the Modeling of Alzheimer's Disease."
   Frontiers in Neuroscience. 16:807473. (2022)
3. Sato K, Watamura N, Fujioka R, Mihira N, Sekiguchi M, Nagata K, Ohshima T, Saito T, Saido TC, Sasaguri H.
   "A third-generation mouse model of Alzheimer's disease shows early and increased cored plaque pathology composed of wild-type human amyloid β peptide."
   Journal of Biological Chemistry. 297(3):101004. (2021)
4. Sato K, Sasaguri H (co-first author), Kumita W, Inoue T, Kurotaki Y, Nagata K, Mihira N, Sato K, Sakuma T, Yamamoto T, Tagami M, Manabe R, Ozaki K, Okazaki Y, Saido TC, Sasaki E.
   "A non-human primate model of familial Alzheimer’s disease."
   bioRxiv. doi: https://doi.org/10.1101/2020.08.24.264259. (2020)
5. Sasaguri H, Nagata K, Sekiguchi M, Fujioka R, Matsuba Y, Hashimoto S, Sato K, Kurup D, Yokota T, Saido TC.
   "Introduction of pathogenic mutations into the mouse Psen1 gene by Base Editor and Target-AID."
   Nature Communications. 9(1):2892. (2018)
6. Sasaguri H, Nilsson P, Hashimoto S, Nagata K, Saito T, De Strooper B, Hardy J, Vassar R, Winblad B, Saido TC.
   "APP mouse models for Alzheimer's disease preclinical studies."
   EMBO Joural. 36(17):2473-2487. (2017)
7. * Sasaguri H, Chew J, Xu YF, Gendron TF, Garrett A, Lee CW, Jansen-West K, Bauer PO, Perkerson EA, Tong J, Stetler C, Zhang YJ.
   "The extreme N-terminus of TDP-43 mediates the cytoplasmic aggregation of TDP-43 and associated toxicity in vivo." Brain Research. 1647:57-64. (2016)
8. * Zhang YJ, Gendron TF, Grima JC, Sasaguri H, Jansen-West K, Xu YF, Katzman RB, Gass J, Murray ME, Shinohara M, Lin WL, Garrett A, Stankowski JN, Daughrity L, Tong J, Perkerson EA, Yue M, Chew J, Castanedes-Casey M, "Kurti A, Wang ZS, Liesinger AM, Baker JD, Jiang J, Lagier-Tourenne C, Edbauer D, Cleveland DW, Rademakers R, Boylan KB, Bu G, Link CD, Dickey CA, Rothstein JD, Dickson DW, Fryer JD, Petrucelli L."
   C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins. Nature Neuroscience. 19(5):668-677. (2016)
9. * Chew J, Gendron TF, Prudencio M, Sasaguri H, Zhang YJ, Castanedes-Casey M, Lee CW, Jansen-West K, Kurti A, Murray ME, Bieniek KF, Bauer PO, Whitelaw EC, Rousseau L, Stankowski JN, Stetler C, Daughrity LM, Perkerson EA, Desaro P, Johnston A, Overstreet K, Edbauer D, Rademakers R, Boylan KB, Dickson DW, Fryer JD, Petrucelli L.
   "Neurodegeneration. C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits."
   Science. 348(6239):1151-4. (2015)
10. * Uchida A, Sasaguri H, Kimura N, Tajiri M, Ohkubo T, Ono F, Sakaue F, Kanai K, Hirai T, Sano T, Shibuya K, Kobayashi M, Yamamoto M, Yokota S, Kubodera T, Tomori M, Sakaki K, Enomoto M, Hirai Y, Kumagai J, Yasutomi Y, Mochizuki H, Kuwabara S, Uchihara T, Mizusawa H, Yokota T.
    "Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43."
    Brain. 135(Pt 3):833-46. (2012)