論文

基本情報

氏名 竹谷 浩介
氏名(カナ) タケヤ コウスケ
氏名(英語) Takeya Kosuke
所属 獣医学部 獣医学科
職名 講師
researchmap研究者コード 5000068922
researchmap機関 岡山理科大学

題名

Overexpression of progranulin increases pathological protein accumulation by suppressing autophagic flux                    

単著・共著の別

共著

著者

Tanaka Y, Kusumoto SY, Honma Y, Takeya K, Eto M

概要

Progranulin (PGRN) haploinsufficiency from autosomal dominant mutations in the PGRN gene causes frontotemporal lobar degeneration, which is characterized by cytoplasmic inclusions predominantly containing TDP-43 (FTLD-TDP). PGRN supplementation for patients with a PGRN gene mutation has recently been proposed as a therapeutic strategy to suppress FTLD-TDP. However, it currently remains unclear whether excessive amounts of PGRN are beneficial or harmful. We herein report the effects of PGRN overexpression on autophagic flux in a cultured cell model. PGRN overexpression increased the level of an autophagosome marker without promoting autophagosome formation and decreased the signal intensity of an autolysosome marker, indicating the suppression of autophagic flux due to reductions in the formation of autolysosomes. Assessments of lysosome numbers and biogenesis using LysoTracker and cells stably expressing TFEB-GFP, respectively, indicated that PGRN overexpression increased the lysosome numbers without lysosomal biogenesis. These results suggest that PGRN overexpression suppressed autophagic flux by inhibiting autophagosome-lysosome fusion. Moreover, PGRN overexpression enhanced polyglutamine aggregation and aggregate-prone TDP-43 accumulation, indicating that the suppression of autophagic flux by excessive amounts of PGRN worsens the pathology of neurodegenerative diseases.    

発表雑誌等の名称

Biochemical and Biophysical Research Communications                        

出版者

611

開始ページ

78

終了ページ

84

発行又は発表の年月

2022/06

査読の有無

有り

招待の有無

無し

記述言語

英語

掲載種別

研究論文(学術雑誌)

ISSN

ID:DOI

10.1016/j.bbrc.2022.04.064

ID:NAID(CiNiiのID)

ID:PMID

35483222

URL

JGlobalID

arXiv ID

ORCIDのPut Code

DBLP ID