Establishment of induced neurons (iN cells) derived from lysosomal disease patients involving neurological symptoms and elucidation of regulatory mechanism of neurodegeneration

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670269
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: The University of Tokushima
• Principal Investigator: ITOH Kohji 徳島大学, 大学院医歯薬学研究部, 教授 (00184656)
• Co-Investigator(Kenkyū-buntansha): TSUJI Daisuke 徳島大学, 大学院医歯薬学研究部, 助教 (00423400) ; IKUO Mariko 徳島大学, 大学院医歯薬学研究部, 特任助教 (60713401)
• Co-Investigator(Renkei-kenkyūsha): URANO Yasuteru 東京大学, 医学(系)研究科(研究院), 教授 (20292956)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ダイレクトリプログラミング / 疾患iPS細胞 / induced Neuron (iN細胞） / リソソーム病 / 蛍光イメージング / トラフィッキング

Outline of Final Research Achievements

This study was performed to establish induced Neurons (iN cells) by direct reprogramming from patient fibroblasts and/or induce neurons from the iPS cells derived from the patient with lysosomal diseases involving neurological symptoms. We succeeded in inducing cortical neurons (CN) from the patient iPS cells with Tay-Sachs disease (TSD, Hexαdeficiency) and cathepsin A (CTSA) deficiency, in which their substrate accumulation was observed. The TSD-CN showed lower cell viability in the absence of neurotrophic factors, that was restored by normal recombinant Hex enzyme replacement. The CN culture system induced from the iPS cells with neurodegenerative lysosomal diseases was considered to be useful for studying the neuropathogenesis and evaluating therapeutic approaches.

Free Research Field

分子病理学・分子治療学