Humanin and colivelin: Neuronal-death-suppressing peptides for Alzheimer's disease and amyotrophic lateral sclerosis

Masaaki Matsuoka, Yuichi Hashimoto, Sadakazu Aiso, Ikuo Nishimoto

研究成果: Review article査読

41 被引用数 (Scopus)

抄録

Humanin (HN), a 24-amino-acid neuroprotective peptide, was originally found in the occipital lobe of an autopsied Alzheimer's disease (AD) patient. HN inhibits neuronal death by binding to its specific receptor on the cell membrane and triggering a Jak2/STAT3 prosurvival pathway. The activation of this pathway may represent a therapeutic approach to AD. HN also exhibits neuroprotective activity against toxicity by familial amyotrophic lateral sclerosis (ALS)-related mutant superoxide dismutase (SOD1). Recent investigations established that AGA-(C8R)-HNG17, a 17-amno-acid derivative of HN, is 10 5 times more potent as a neuroprotective than HN; at 10-picomolar and higher concentrations in vitro it completely suppresses neuronal death. Moreover, a 26-amino-acid peptide colivelin (CL), composed of activity-dependent neurotrophic factor (ADNF) C-terminally fused to AGA-(C8R)-HNG17, provides complete neuroprotection at 100-femtomolar or higher concentrations in vitro. A series of experiments using mouse AD and ALS models further established the efficacy of HN derivatives, including CL, against these diseases in vivo. HN and CL can be viewed as drug candidates for neuronal death suppression therapy in AD or ALS.

本文言語English
ページ(範囲)113-122
ページ数10
ジャーナルCNS Drug Reviews
12
2
DOI
出版ステータスPublished - 2006 6
外部発表はい

ASJC Scopus subject areas

  • 神経心理学および生理心理学
  • 薬理学

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