オオヤマ　ゲンコウ   OYAMA Genko   大山　彦光    所属   埼玉医科大学  医学部 脳神経内科    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読なし
表題	Reduced astrocytic reactivity in human brains and midbrain organoids with PRKN mutations.
掲載誌名	正式名：NPJ Parkinson's disease
掲載区分	国外
巻・号・頁	6(1),33-33頁
著者・共著者	Masayoshi Kano,Masashi Takanashi,Genko Oyama,Asako Yoritaka,Taku Hatano,Kahori Shiba-Fukushima,Makiko Nagai,Kazutoshi Nishiyama,Kazuko Hasegawa,Tsuyoshi Inoshita,Kei-Ichi Ishikawa,Wado Akamatsu,Yuzuru Imai,Silvia Bolognin,Jens Christian Schwamborn,Nobutaka Hattori
発行年月	2020/11/13
概要	Parkin (encoded by PRKN) is a ubiquitin ligase that plays an important role in cellular mitochondrial quality control. Mutations in PRKN cause selective dopaminergic cell loss in the substantia nigra and are presumed to induce a decrease in mitochondrial function caused by the defective clearance of mitochondria. Several studies have demonstrated that parkin dysfunction causes mitochondrial injury and astrocytic dysfunction. Using immunohistochemical methods, we analyzed astrocytic changes in human brains from individuals with PRKN mutations. Few glial fibrillary acidic protein- and vimentin-positive astrocytes were observed in the substantia nigra in PRKN-mutated subjects compared with subjects with idiopathic Parkinson's disease. We also differentiated patient-specific induced pluripotent stem cells into midbrain organoids and confirmed decreased numbers of glial fibrillary acidic protein-positive astrocytes in PRKN-mutated organoids compared with age- and sex-matched controls. Our study reveals PRKN-mutation-induced astrocytic alteration and suggests the possibility of an astrocyte-related non-autonomous cell death mechanism for dopaminergic neurons in brains of PRKN-mutated patients.
DOI	10.1038/s41531-020-00137-8
PMID	33298969