The crucial role of caspase-9 in the disease progression of a transgenic ALS mouse model

Haruhisa Inoue, Kayoko Tsukita, Takuji Iwasato, Yasuyuki Suzuki, Masanori Tomioka, Minako Tateno, Masahiro Nagao, Akihiro Kawata, Takaomi C. Saido, Masayuki Miura, Hidemi Misawa, Shigeyoshi Itohara, Ryosuke Takahashi

研究成果: Article査読

94 被引用数 (Scopus)


Mutant copper/zinc superoxide dismutase (SOD1)-overexpressing transgenic mice, a mouse model for familial amyotrophic lateral sclerosis (ALS), provides an excellent resource for developing novel therapies for ALS. Several observations suggest that mitochondria-dependent apoptotic signaling, including caspase-9 activation, may play an important role in mutant SOD1-related neurodegeneration. To elucidate the role of caspase-9 in ALS, we examined the effects of an inhibitor of X chromosome-linked inhibitor of apoptosis (XIAP), a mammalian inhibitor of caspase-3, -7 and -9, and p35, a baculoviral broad caspase inhibitor that does not inhibit caspase-9. When expressed in spinal motor neurons of mutant SOD1 mice using transgenic techniques, XIAP attenuated disease progression without delaying onset. In contrast, p35 delayed onset without slowing disease progression. Moreover, caspase-9 was activated in spinal motor neurons of human ALS subjects. These data strongly suggest that caspase-9 plays a crucial role in disease progression of ALS and constitutes a promising therapeutic target.

ジャーナルEMBO Journal
出版ステータスPublished - 2003 12月 15

ASJC Scopus subject areas

  • 神経科学(全般)
  • 分子生物学
  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)


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