Humanin antagonists: Mutants that interfere with dimerization inhibit neuroprotection by Humanin

Yuichi Hashimoto, Kenzo Terashita, Takako Niikura, Yohichi Yamagishi, Miho Ishizaka, Kohsuke Kanekura, Tomohiro Chiba, Marina Yamada, Yoshiko Kita, Sadakazu Aiso, Masaaki Matsuoka, Ikuo Nishimoto

研究成果: Article査読

17 被引用数 (Scopus)

抄録

The 24-residue peptide Humanin (HN) protects neuronal cells from insults of various Alzheimer's disease (AD) genes and Aβ by forming a homodimer. We have previously shown that P3A, S7A, C8A, L9A, L12A, T13A, S14A and P19A mutations nullify the neuroprotective function of HN [Yamagishi, Y, Hashimoto, Y., Niikura, T. & Nishimoto, I. (2003) Peptides, 24, 585-595]. Here we examined whether any of these 'null' mutants could function as dominant-negative mutants. Homodimerization-defective mutants, P3A-, L12A-, S14A- and P19A-HN, specifically blocked neuroprotection by HN, but not by activity-dependent neurotrophic factor. Furthermore, insertion of S7A, the mutation that blocks the homodimerization of HN, but not insertion of G5A abolished the antagonizing function of L12A-HN. While L12A-HN and G5A/L12A-HN actually inhibited HN homodimerization, S7A/L12A-HN had no effect. These data indicate that P3A-, L12A-, S14A- and P19A-HN function as HN antagonists by forming an inactive dimer with HN. This study provides a novel insight into the understanding of the in vivo function of HN, as well as into the development of clinically applicable HN neutralizers.

本文言語English
ページ(範囲)2356-2364
ページ数9
ジャーナルEuropean Journal of Neuroscience
19
9
DOI
出版ステータスPublished - 2004 5
外部発表はい

ASJC Scopus subject areas

  • 神経科学(全般)

フィンガープリント

「Humanin antagonists: Mutants that interfere with dimerization inhibit neuroprotection by Humanin」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル