Paeoniflorin eliminates a mutant AR via NF-YA-dependent proteolysis in spinal and bulbar muscular atrophy

Genki Tohnai, Hiroaki Adachi, Masahisa Katsuno, Hideki Doi, Shinjiro Matsumoto, Naohide Kondo, Yu Miyazaki, Madoka Iida, Hideaki Nakatsuji, Qiang Qiang, Ying Ding, Hirohisa Watanabe, Masahiko Yamamoto, Kenzo Ohtsuka, Gen Sobue

研究成果: Article査読

20 被引用数 (Scopus)

抄録

The accumulation of abnormal proteins is a common characteristic of neurodegenerative diseases. This accumulation reflects a severe disturbance of cellularhomeostasis in pathogenic protein clearance. Here,wedemonstrated that the activation of the two major proteolytic machineries, the molecular chaperone-ubiquitin proteasome system (UPS) and the autophagy system, were simultaneously enhanced by paeoniflorin (PF), a major component of Paeonia plants, and exerted therapeutic effects in models of spinal and bulbar muscular atrophy (SBMA). PF significantly increased the expression of nuclear factor-YA (NF-YA), which strongly upregulated the molecules involved in the proteolytic machinery [molecular chaperones, carboxyl terminus of Hsc70-interacting protein and transcription factor EB], which thus mitigated the behavioral and pathological impairments in an SBMA mouse model through the upregulation of pathogenic androgen receptor protein clearance in motor neurons and muscles. These findings demonstrated that PF is able to enhance both the UPS and autophagy systems by upregulating the expression of NF-YA, which promotes therapeutic effects in an SBMA model.

本文言語English
論文番号ddu066
ページ(範囲)3552-3565
ページ数14
ジャーナルHuman molecular genetics
23
13
DOI
出版ステータスPublished - 07-2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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