Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection

Yuichi Hashimoto, Hiroaki Suzuki, Sadakazu Aiso, Takako Niikura, Ikuo Nishimoto, Masaaki Matsuoka

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Humanin (HN) inhibits neuronal cell death induced by various Alzheimer's disease (AD)-related insults. It has been proposed that HN binds to a putative receptor on the cell membrane and triggers a signal transduction cascade linked to neuroprotection. Recently, it was shown that HN binds to pertussis toxin (PTX)-sensitive G protein-coupled formylpeptide receptor-like-1 molecule (FPRL-1), reduces Aβ(1-42) aggregation and fibril formation, and suppresses the Aβ(1-42) toxicity on mononuclear phagocytic cells [Ying, G., Iribarren, P., Zhou, Y., Gong, W., Zhang, N., Yu, Z.X., Le, Y., Cui, Y., Wang, J.M., 2004. Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. Journal of Immunology 172 (11), 7078-7085.]. We here show that siRNA-mediated disruption of expression of the mouse counterpart of FPRL-1, FPR2, did not result in attenuation of HN-mediated rescue of neuronal cell death induced by AD-related insults. We simultaneously provide evidence that neuroprotection by HN in F11 cells is mediated by the STAT3 transcription factor as well as by certain tyrosine kinases. Altogether, we speculate that a receptor other than FPR2 exists that mediates HN neuroprotection in F11 neurohybrid cells

Original languageEnglish
Pages (from-to)3092-3104
Number of pages13
JournalLife Sciences
Volume77
Issue number24
DOIs
Publication statusPublished - 2005 Oct 28

Keywords

  • Alzheimer's disease
  • FPR2
  • FPRL-1
  • Humanin
  • Neuronal cell death
  • STAT3
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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  • Cite this

    Hashimoto, Y., Suzuki, H., Aiso, S., Niikura, T., Nishimoto, I., & Matsuoka, M. (2005). Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection. Life Sciences, 77(24), 3092-3104. https://doi.org/10.1016/j.lfs.2005.03.031