Proteasome impairment in neural cells derived from HMSN-P patient iPSCs

• 資料種別: 博士論文
• ISSN: 1756-6606
• タイトル: Proteasome impairment in neural cells derived from HMSN-P patient iPSCs
• 巻次・部編番号: 10
• 著者・編者: Murakami, Nagahisa; Imamura, Keiko; Izumi, Yuishin; Egawa, Naohiro; Tsukita, Kayoko; Enami, Takako; Yamamoto, Takuya; Kawarai, Toshitaka; Kaji, Ryuji; Inoue, Haruhisa
• 著者標目: Murakami, Nagahisa; Imamura, Keiko; Izumi, Yuishin; Egawa, Naohiro; Tsukita, Kayoko; Enami, Takako; Yamamoto, Takuya; Kawarai, Toshitaka; Kaji, Ryuji; Inoue, Haruhisa
• 出版事項: Springer nature
• 出版年月日等: 2017-02-15
• 出版年（W3CDTF）: 2017-02-15
• 並列タイトル等: 近位筋優位運動感覚ニューロパチー(HMSN-P)患者iPS細胞から分化した神経細胞はプロテアソーム障害を認める
• タイトル（掲載誌）: Molecular Brain
• 授与機関名: 徳島大学
• 授与年月日: 2017-04-27
• 授与年月日（W3CDTF）: 2017-04-27
• 報告番号: 甲第3094号
• 学位: 博士（医学）
• 博論授与番号: 甲第3094号
• 本文の言語コード: eng
• 件名標目: HMSN-P; TFG; UPS; iPSCs; Gene correction; CRISPR-Cas9; Neurodegeneration
• 対象利用者: 一般
• 一般注記: Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is caused by a heterozygous mutation (P285L) in Tropomyosin-receptor kinase Fused Gene (TFG), histopathologically characterized by progressive spinal motor neuron loss with TFG cytosolic aggregates. Although the TFG protein, found as a type of fusion oncoprotein, is known to facilitate vesicle transport from endoplasmic reticulum (ER) to Golgi apparatus at ER exit site, it is unclear how mutant TFG causes motor neuron degeneration. Here we generated induced pluripotent stem cells (iPSCs) from HMSN-P patients, and differentiated the iPSCs into neural cells with spinal motor neurons (iPS-MNs). We found that HMSN-P patient iPS-MNs exhibited ubiquitin proteasome system (UPS) impairment, and HMSN-P patient iPS-MNs were vulnerable to UPS inhibitory stress. Gene correction of the mutation in TFG using the CRISPR-Cas9 system reverted the cellular phenotypes of HMSN-P patient iPS-MNs. Collectively, these results suggest that our cellular model with defects in cellular integrity including UPS impairments may lead to identification of pathomechanisms and a therapeutic target for HMSN-P.
• DOI: info:doi/10.1186/s13041-017-0286-y; https://doi.org/info:doi/10.1186/s13041-017-0286-y
• 国立国会図書館永続的識別子: info:ndljp/pid/10371161; https://dl.ndl.go.jp/pid/10371161
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2017-07-03T04:10:06+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://repo.lib.tokushima-u.ac.jp/110142
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp