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

Masaaki Matsuoka, Yuichi Hashimoto, Sadakazu Aiso, Ikuo Nishimoto

Research output: Contribution to journalReview article

40 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalCNS Drug Reviews
Volume12
Issue number2
DOIs
Publication statusPublished - 2006 Jun 1

Keywords

  • Alzheimer's disease
  • Amyotrophic lateral sclerosis
  • Colivelin
  • Humanin
  • β-Amyloid

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Pharmacology

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